NM_000256.3:c.1927+215C>T

Variant names:

• chr11-47340788-G-A
• rs10769253
• NM_000256.3:c.1927+215C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000256.3(MYBPC3):​c.1927+215C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,176 control chromosomes in the GnomAD database, including 6,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (6104 hom., cov: 34)
• Consequence: MYBPC3 NM_000256.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0830
• Publications: 16 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-47340788-G-A is Benign according to our data. Variant chr11-47340788-G-A is described in ClinVar as Benign. ClinVar VariationId is 672523.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBPC3	NM_000256.3	c.1927+215C>T		intron_variant	Intron 20 of 34	ENST00000545968.6	NP_000247.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYBPC3	ENST00000545968.6	c.1927+215C>T		intron_variant	Intron 20 of 34	5	NM_000256.3	ENSP00000442795.1
MYBPC3	ENST00000399249.6	c.1927+215C>T		intron_variant	Intron 19 of 33	5		ENSP00000382193.2
MYBPC3	ENST00000544791.1	n.1927+215C>T		intron_variant	Intron 20 of 26	5		ENSP00000444259.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39740 AN: 152056 Hom.: 6104 Cov.: 34

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.218

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.261 AC: 39750 AN: 152176 Hom.: 6104 Cov.: 34 AF XY: 0.270 AC XY: 20047 AN XY: 74380

African (AFR) AF: 0.367 AC: 15235 AN: 41522

American (AMR) AF: 0.271 AC: 4141 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 631 AN: 3470

East Asian (EAS) AF: 0.579 AC: 3002 AN: 5182

South Asian (SAS) AF: 0.234 AC: 1131 AN: 4826

European-Finnish (FIN) AF: 0.298 AC: 3153 AN: 10576

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11847 AN: 67992

Other (OTH) AF: 0.214 AC: 453 AN: 2112

Alfa AF: 0.199 Hom.: 13776

Bravo AF: 0.267

Asia WGS AF: 0.319 AC: 1108 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.21
PhyloP100		0.083
Mutation Taster		=88/12	polymorphism (auto)

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: rs10769253; hg19: chr11-47362339;