chr11-47331829-G-C

Variant names:

• chr11-47331829-G-C
• rs371789899
• NM_000256.3:c.*26+16C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_000256.3(MYBPC3):​c.*26+16C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000479 in 1,597,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00048 (0 hom.)
• Consequence: MYBPC3 NM_000256.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.162
• Publications: 0 publications found

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]

MYBPC3 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• hypertrophic cardiomyopathy 4

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• left ventricular noncompaction 10

  Inheritance: AR, AD Classification: DEFINITIVE, MODERATE, LIMITED Submitted by: Ambry Genetics
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• atrial fibrillation

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-47331829-G-C is Benign according to our data. Variant chr11-47331829-G-C is described in ClinVar as [Benign]. Clinvar id is 1247492.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBPC3	NM_000256.3	c.*26+16C>G		intron_variant	Intron 34 of 34	ENST00000545968.6	NP_000247.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYBPC3	ENST00000545968.6	c.*26+16C>G		intron_variant	Intron 34 of 34	5	NM_000256.3	ENSP00000442795.1
MYBPC3	ENST00000399249.6	c.*26+16C>G		intron_variant	Intron 33 of 33	5		ENSP00000382193.2

Frequencies

GnomAD3 genomes AF: 0.000434 AC: 66 AN: 152220 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000823

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000313 AC: 70 AN: 223862 AF XY: 0.000312

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000125

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000637

Gnomad OTH exome AF: 0.000362

GnomAD4 exome AF: 0.000484 AC: 700 AN: 1445492 Hom.: 0 Cov.: 30 AF XY: 0.000463 AC XY: 332 AN XY: 717696

African (AFR) AF: 0.000120 AC: 4 AN: 33212

American (AMR) AF: 0.0000936 AC: 4 AN: 42726

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25742

East Asian (EAS) AF: 0.00 AC: 0 AN: 39070

South Asian (SAS) AF: 0.00 AC: 0 AN: 83650

European-Finnish (FIN) AF: 0.0000195 AC: 1 AN: 51270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5430

European-Non Finnish (NFE) AF: 0.000616 AC: 680 AN: 1104700

Other (OTH) AF: 0.000184 AC: 11 AN: 59692

GnomAD4 genome AF: 0.000433 AC: 66 AN: 152338 Hom.: 0 Cov.: 33 AF XY: 0.000362 AC XY: 27 AN XY: 74490

African (AFR) AF: 0.000168 AC: 7 AN: 41578

American (AMR) AF: 0.000131 AC: 2 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000823 AC: 56 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000144 Hom.: 0

Bravo AF: 0.000408

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.61
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs371789899; hg19: chr11-47353380;