11-47342611-C-G

Position:

• chr11-47342611-C-G

Variant summary

Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PS1 PM1 PP3_Strong PP5_Very_Strong

The NM_000256.3(MYBPC3):​c.1591G>C​(p.Gly531Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,612,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin Lovd. Synonymous variant affecting the same amino acid position (i.e. G531G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: MYBPC3 NM_000256.3 missense
• Clinical Significance: Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:18
• Conservation: PhyloP100: 7.50

Genes affected

MYBPC3 (HGNC:7551): (myosin binding protein C3) MYBPC3 encodes the cardiac isoform of myosin-binding protein C. Myosin-binding protein C is a myosin-associated protein found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. MYBPC3 is expressed exclusively in heart muscle and is a key regulator of cardiac contraction. Mutations in this gene are a frequent cause of familial hypertrophic cardiomyopathy. [provided by RefSeq, May 2022]

ACMG classification

Verdict is Pathogenic. Variant got 18 ACMG points.

• PS1: Transcript NM_000256.3 (MYBPC3) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in Lovd
• PM1: In a domain Ig-like C2-type 3 (size 90) in uniprot entity MYPC3_HUMAN there are 33 pathogenic changes around while only 9 benign (79%) in NM_000256.3
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.954
• PP5: Variant 11-47342611-C-G is Pathogenic according to our data. Variant chr11-47342611-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 42550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-47342611-C-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYBPC3	NM_000256.3	c.1591G>C	p.Gly531Arg	missense_variant	17/35	ENST00000545968.6	NP_000247.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYBPC3	ENST00000545968.6	c.1591G>C	p.Gly531Arg	missense_variant	17/35	5	NM_000256.3	ENSP00000442795.1
MYBPC3	ENST00000399249.6	c.1591G>C	p.Gly531Arg	missense_variant	16/34	5		ENSP00000382193.2
MYBPC3	ENST00000544791.1	n.1591G>C		non_coding_transcript_exon_variant	17/27	5		ENSP00000444259.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000121 AC: 3 AN: 247086 Hom.: 0 AF XY: 0.0000149 AC XY: 2 AN XY: 134034

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000269

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1460130 Hom.: 0 Cov.: 31 AF XY: 0.0000207 AC XY: 15 AN XY: 726248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000198

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152326 Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2 AN XY: 74492

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000224 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.0000546

EpiControl AF: 0.0000595

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:18

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hypertrophic cardiomyopathy 4 Pathogenic:5

Pathogenic, criteria provided, single submitter	clinical testing	Laboratory of Medical Genetics, National & Kapodistrian University of Athens	May 16, 2022	PS1, PM2, PM1, PP3, PP5 -
Likely pathogenic, criteria provided, single submitter	clinical testing	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	Oct 08, 2024	Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with hypertrophic cardiomyopathy 4 (HCM; MIM#115197). (I) 0108 - This gene is associated with both recessive and dominant disease. Dominant inheritance is frequently reported in adult-onset conditions and recessive inheritance results in a more severe early onset phenotype (OMIM). (I) 0115 - Variants in this gene are known to have variable expressivity (PMID: 32841044). (I) 0200 - Variant is predicted to result in a missense amino acid change from glycine to arginine. (I) 0252 - This variant is homozygous. (I) 0304 - Variant is present in gnomAD (v2 and v3 (non-v2)) <0.01 for a recessive condition (8 heterozygotes, 0 homozygotes). A different nucleotide substitution resulting in the same amino acid change has also been observed in gnomAD (v2 and v3 (non-v2): 12 heterozygotes, 0 homozygotes). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v3) (p.(Gly531Trp): 1 heterozygote, 0 homozygotes). (I) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated Immunoglobulin I-set domain 3 domain (DECIPHER; PMID: 32841044). (I) 0710 - Another missense variant comparable to the one identified in this case has inconclusive previous evidence for pathogenicity. The p.(Gly531Trp) variant has been classified as a VUS by multiple clinical diagnostic laboratories (ClinVar). (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant (G>C) and a different nucleotide substitution (G>A), which result in the same amino acid change, have been classified as likely pathogenic and pathogenic by multiple clinical diagnostic laboratories and have been reported in multiple individuals with HCM (ClinVar; Atlas of Cardiac Genetic Variation; PMIDs: 21750094, 24793961, 28356264, 31941943, 32841044, 36291626). Additionally, this amino acid change has also been classified as a VUS by two clinical diagnostic laboratories and has also been reported in one individual with left ventricular noncompaction cardiomyopathy (ClinVar; PMID: 28798025). (SP) 1002 - This variant has moderate functional evidence supporting abnormal protein function. Mutant constructs transfected into knockout engineered heart cells mice tissues and expressed either as heterozygous or homozygous demonstrated abnormal force and contraction velocity compared to WT (PMID: 27108529). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign -
Likely pathogenic, criteria provided, single submitter	clinical testing	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	Mar 20, 2023	homozygous case; clinical and carrier status of parents are unkown -
Pathogenic, criteria provided, single submitter	clinical testing	Institute of Human Genetics, University of Leipzig Medical Center	Mar 31, 2023	This variant was identified as compound heterozygous with NM_000256.3:c.1591G>C._x000D_ Criteria applied: PS1, PS4, PM2_SUP, PP3 -
Likely pathogenic, criteria provided, single submitter	clinical testing	Clinical Genetics Laboratory, Skane University Hospital Lund	Nov 21, 2024	ACMG criterias used: PS3, PS4, PM2 and PP3. -

Hypertrophic cardiomyopathy Pathogenic:4

Likely pathogenic, criteria provided, single submitter	clinical testing	National Institute of Allergy and Infectious Diseases - Centralized Sequencing Program, National Institutes of Health	Aug 06, 2021	- -
Likely pathogenic, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jul 19, 2023	The p.Gly531Arg variant in MYBPC3 has been reported in association with two distinct nucleotide changes: c.1591G>C and c.1591G>A. Considering both nucleotide changes, this variant has been reported in 1 individual with dilated cardiomyopathy (DCM; c.1591G>A; Waldmuller 2011 PMID: 21750094) and in over 10 individuals with hypertrophic cardiomyopathy (HCM; c.1591G>A: Girolami 2006 PMID: 16858239, Olivotto 2008 PMID: 18533079, Garcia-Castro 2009 PMID: 19150014, Michels 2011, Waldmuller 2011 PMID: 21750094, Walsh 2017 PMID: 27532257, LMM data; c.1591G>C: Millat 2010 PMID: 20624503, Olivotto 2011 PMID: 21835320, Coto 2012 PMID: 22765922, Rubattu 2016 PMID: 27483260, LMM data). Of the individuals with HCM, at least 4 individuals carried a second pathogenic MYBPC3 variant and had early onset disease (LMM data, Millat 2010 PMID: 20624503, Rubattu 2016 PMID: 27483260). Furthermore, the c.1591G>C variant was found by our laboratory to segregate with disease in 2 affected relatives from 1 family. This variant has also been reported by other clinical laboratories in ClinVar (Variation IDs: 164109 (c.1591G>A) and 42550 (c.1591G>C)). Additionally, the c.1591G>A variant has been identified in 0.01% (2/15288) of Latino and in 0.002% (1/41450) of African/African American chromosomes by gnomAD, while the c.1591G>C variant has been identified in 0.004% (3/68034) of European chromosomes in gnomAD (https://gnomad.broadinstitute.org, v.3.1.2). A functional study in which the c.1591G>C (p.Gly531Arg) variant was transfected into MYBPC3 knockout mouse cardiomyocytes alone and in combination with wild-type MYBPC3 (to represent homozygous and heterozygous disease states) revealed abnormal contractile force in both scenarios compared to wild-type (Wijnker 2016 PMID: 27108529). Computational prediction tools and conservation analysis also suggest that the variant may impact the protein. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant HCM. ACMG/AMP Criteria applied: PS4_Moderate, PM2_Supporting, PS3_Moderate, PP3. -
Likely pathogenic, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 19, 2023	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 531 of the MYBPC3 protein (p.Gly531Arg). This variant is present in population databases (rs397515912, gnomAD 0.004%). This missense change has been observed in individuals with hypertrophic cardiomyopathy (PMID: 18533079, 20624503, 21750094, 23508784, 24793961, 25524337, 27483260, 27532257, 27600940, 28356264, 30297972). ClinVar contains an entry for this variant (Variation ID: 42550). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. -
Likely pathogenic, criteria provided, single submitter	clinical testing	All of Us Research Program, National Institutes of Health	Sep 23, 2024	This missense variant replaces glycine with arginine at codon 531 of the MYBPC3 protein. Computational prediction tools and conservation analyses suggest that this variant may have a deleterious impact on the protein function. In heart tissue engineered from mouse cardiac cells, this variant in heterozygous state was associated with a hypercontractile phenotype (PMID: 27108529). This variant has been reported in over ten unrelated individuals affected with hypertrophic cardiomyopathy (PMID: 16858239, 18533079, 20173211, 20624503, 21835320, 23508784, 23690394, 27483260, 27532257, 27600940, 28193612, 28241245, 28986452, 31941943, 32228044, 32369506, 36291626). Two of these individuals carried a second pathogenic variant either in the same gene (PMID: 20624503) or in another gene (PMID: 32228044). This variant has also been reported in an individual affected with left ventricular non-compaction (PMID: 28798025). This variant has been identified in 5/278462 chromosomes in the general population by the Genome Aggregation Database (gnomAD). A different variant causing the same amino acid change, c.1591G>A p.Gly531Arg, is also considered to be disease-causing (ClinVar variation ID: 164109). In summary, this variant has shown a relevant phenotype in an experimental study and has been observed in multiple individuals affected with hypertrophic cardiomyopathy. Based on available evidence, this variant is classified as Likely Pathogenic. -

not provided Pathogenic:3

Likely pathogenic, criteria provided, single submitter	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Apr 12, 2024	PP3, PM2, PM3_supporting, PS3_supporting, PS4_moderate -
Likely pathogenic, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	MYBPC3: PS1, PS3:Supporting, PS4:Supporting -
Likely pathogenic, criteria provided, single submitter	clinical testing	GeneDx	Sep 25, 2024	Identified in patients with cardiomyopathy referred for genetic testing at GeneDx and in published literature, although clinical details were often limited (PMID: 21835320, 25351510, 27483260, 27532257, 22765922, 16858239, 32841044, 35208637, 36291626, 20624503, 36252119, 36264615, 37652022); Not observed at significant frequency in large population cohorts (gnomAD); Functional studies examining the effect of c.1591 G>C in mouse-derived engineered heart tissue demonstrated that tissue expressing the variant is associated with a hypercontractile phenotype compared to wild type cardiac tissue (PMID: 27108529); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28241245, 25351510, 23690394, 19150014, 27532257, 23508784, 27483260, 28193612, 16858239, 22765922, 21835320, 28798025, 34426522, 32841044, 35208637, 35753512, 35433691, 36291626, 35130036, 20624503, 36264615, 36252119, 37652022, 36243179, 27108529) -

Cardiomyopathy Pathogenic:2

Likely pathogenic, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Aug 30, 2023	This missense variant replaces glycine with arginine at codon 531 of the MYBPC3 protein. Computational prediction tools and conservation analyses suggest that this variant may have a deleterious impact on the protein function. In heart tissue engineered from mouse cardiac cells, this variant in heterozygous state was associated with a hypercontractile phenotype (PMID: 27108529). This variant has been reported in over ten unrelated individuals affected with hypertrophic cardiomyopathy (PMID: 16858239, 18533079, 20173211, 20624503, 21835320, 23508784, 23690394, 27483260, 27532257, 27600940, 28193612, 28241245, 28986452, 31941943, 32228044, 32369506, 36291626). Two of these individuals carried a second pathogenic variant either in the same gene (PMID: 20624503) or in another gene (PMID: 32228044). This variant has also been reported in an individual affected with left ventricular non-compaction (PMID: 28798025). This variant has been identified in 5/278462 chromosomes in the general population by the Genome Aggregation Database (gnomAD). A different variant causing the same amino acid change, c.1591G>A p.Gly531Arg, is also considered to be disease-causing (ClinVar variation ID: 164109). In summary, this variant has shown a relevant phenotype in an experimental study and has been observed in multiple individuals affected with hypertrophic cardiomyopathy. Based on available evidence, this variant is classified as Likely Pathogenic. -
Pathogenic, criteria provided, single submitter	clinical testing	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	May 31, 2022	- -

Hypertrophic cardiomyopathy;C0043202:Wolff-Parkinson-White pattern Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Agnes Ginges Centre for Molecular Cardiology, Centenary Institute

Feb 09, 2018

MYBPC3 Gly531Arg variant has been reported as two nucleotide changes: c.1591G>C and c.1591G>A. When considered together this variant has been identified in 1 DCM proband (Waldmuller S, et al., 2011) and more than 10 individuals with HCM and no other pathogenic variants (Girolami F, et al., 2006; Ho CY, et al., 2009; Michels M, 2011; Waldmuller S, et al., 2011; Olivotto I, et al., 2011; Coto E, et al., 2012; Bos JM, et al., 2014; Lopes LR, et al., 2015; Rubattu S, et al., 2016; Walsh R, et al., 2017; LMM, Pers. Comm.; GeneDx, Pers. Comm.) The variant has also been found to segregate with disease in at least 1 family (LMM, Pers. Comm.). We have identified the c.1591G>C in 2 HCM probands. One proband has family history of disease in their sibling, but segregation was not possible. In the other family, the proband also harbors a second likely pathogenic TNNT2 Phe110Leu. This variant is present at a low frequency in the Genome Aggregation Database (MAF= 0.000022; http://gnomad.broadinstitute.org/). In vitro functional studies show that p.Gly531Arg causes hypercontractility in engineered heart tissue (Wijnker PJ, et al., 2016). In silico tools SIFT, PolyPhen-2 and MutationTaster predict the variant to be deleterious. In summary, the variant has been reported in numerous cases, it is rare in the general population, functional studies and in silico tools predict the variant to impact protein function, therefore we classify MYBPC3 Gly531Arg as 'Likely Pathogenic'. -

Hypertrophic cardiomyopathy 4;C3715165:Left ventricular noncompaction 10 Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 10, 2021

- -

Primary familial hypertrophic cardiomyopathy Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Jun 02, 2022

Variant summary: MYBPC3 c.1591G>C (p.Gly531Arg) results in a non-conservative amino acid change located in the Immunoglobulin subtype 2 domain (IPR003598) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 247086 control chromosomes (gnomAD). c.1591G>C has been reported in the literature in individuals affected with Hypertrophic Cardiomyopathy (e.g. Girolami_2006, Olivotto_2011, Coppini_2014, Rubattu_2016, Ho_2018). These data indicate that the variant may be associated with disease. Co-occurrences with other pathogenic variant have been reported (MYBPC3 c.2309-2A>G, Rubattu_2016), providing supporting evidence for a benign role. At least one publication reports experimental evidence evaluating an impact on protein function, via measuring contraction forces in an engineered heart tissue assay from MYBPC3-knock out mice. Human wild-type and variant MYBPC3 was transduced into the engineered heart tissue and contraction was assayed at varying Ca2+ levels. The variant failed to rescue the hypercontractile phenotype seen in non-transduced (MYBPC3 null) samples, when expressed either alone or jointly with wild-type MYBPC3, demonstrating the variant may also act in a dominant-negative manner (Wijnker_2016). Seven ClinVar submitters have assessed the variant since 2014: all seven classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. -

Cardiovascular phenotype Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 30, 2024

The p.G531R variant (also known as c.1591G>C), located in coding exon 17 of the MYBPC3 gene, results from a G to C substitution at nucleotide position 1591. The glycine at codon 531 is replaced by arginine, an amino acid with dissimilar properties. This variant and another variant leading to the same amino acid substitution (MYBPC3 c.1591G>A) have been reported in multiple unrelated patients with hypertrophic cardiomyopathy (HCM) (Girolami F et al. J Cardiovasc Med (Hagerstown), 2006 Aug;7:601-7; Olivotto I et al. Mayo Clin Proc, 2008 Jun;83:630-8; García-Castro M et al. Rev Esp Cardiol, 2009 Jan;62:48-56; Ho CY et al. Circ Cardiovasc Genet, 2009 Aug;2:314-21; Millat G et al. Eur J Med Genet, 2010 Jul;53:261-7; Waldmüller S et al. Eur J Heart Fail, 2011 Nov;13:1185-92; Lopes LR et al. Heart, 2015 Feb;101:294-301; Rubattu S et al. Int J Mol Sci, 2016 Jul;17:[ePub ahead of print]; Walsh R et al. Genet Med, 2017 Feb;19:192-203; external communication; Ambry internal data). In a functional study utilizing engineered heart tissue derived from MYBPC3 knockout cardiomyocytes, c.1591G>C p.G531R was unable to completely rescue the hypercontractile phenotype of the knockout tissue; however, the physiological relevance of this result is unclear (Wijnker PJ et al. J. Mol. Cell. Cardiol. 2016;97:82-92). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
CardioboostCm	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.38
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.78	D;T;T
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Pathogenic	0.69	D
MetaRNN	Pathogenic	0.95	D;D;D
MetaSVM	Uncertain	0.53	D
MutationAssessor	Uncertain	2.5	M;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-7.0	D;D;D
REVEL	Pathogenic	0.85
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Vest4		0.99
MVP		0.93
MPC		0.91
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.61
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs397515912; hg19: chr11-47364162;