rs12462762

chr19-50438432-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MYBPC2	NM_004533.4	c.572+714G>A		intron_variant		ENST00000357701.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBPC2	ENST00000357701.6	c.572+714G>A		intron_variant		1	NM_004533.4	P1

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

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.362

Alfa AF: 0.315 Hom.: 5219

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

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: rs12462762; hg19: chr19-50941689;