rs12462762

Variant names:

• chr19-50438432-G-A
• rs12462762
• NM_004533.4:c.572+714G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004533.4(MYBPC2):​c.572+714G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 151,920 control chromosomes in the GnomAD database, including 8,541 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (8541 hom., cov: 31)
• Consequence: MYBPC2 NM_004533.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.136
• Publications: 4 publications found

Genes affected

MYBPC2 (HGNC:7550): (myosin binding protein C2) This gene encodes a member of the myosin-binding protein C family. This family includes the fast-, slow- and cardiac-type isoforms, each of which is a myosin-associated protein found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. The protein encoded by this locus is referred to as the fast-type isoform. Mutations in the related but distinct genes encoding the slow-type and cardiac-type isoforms have been associated with distal arthrogryposis, type 1 and hypertrophic cardiomyopathy, respectively. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBPC2	NM_004533.4	c.572+714G>A		intron_variant	Intron 7 of 27	ENST00000357701.6	NP_004524.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYBPC2	ENST00000357701.6	c.572+714G>A		intron_variant	Intron 7 of 27	1	NM_004533.4	ENSP00000350332.4

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50389 AN: 151802 Hom.: 8534 Cov.: 31

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.332 AC: 50443 AN: 151920 Hom.: 8541 Cov.: 31 AF XY: 0.335 AC XY: 24884 AN XY: 74236

African (AFR) AF: 0.375 AC: 15507 AN: 41392

American (AMR) AF: 0.362 AC: 5524 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 994 AN: 3466

East Asian (EAS) AF: 0.365 AC: 1889 AN: 5172

South Asian (SAS) AF: 0.361 AC: 1735 AN: 4806

European-Finnish (FIN) AF: 0.303 AC: 3206 AN: 10566

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20516 AN: 67954

Other (OTH) AF: 0.362 AC: 767 AN: 2116

Alfa AF: 0.317 Hom.: 19463

Bravo AF: 0.338

Asia WGS AF: 0.373 AC: 1303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.76
PhyloP100		0.14
Mutation Taster		=100/0	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: rs12462762; hg19: chr19-50941689;