19-50433121-C-T

Variant names:

• chr19-50433121-C-T
• rs3765069
• NM_004533.4:c.19+149C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004533.4(MYBPC2):​c.19+149C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 989,436 control chromosomes in the GnomAD database, including 84,795 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 0.37 (11510 hom., cov: 31)
  • Exomes 𝑓: 0.41 (73285 hom.)
• Consequence: MYBPC2 NM_004533.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.218

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBPC2	NM_004533.4	c.19+149C>T		intron_variant	Intron 1 of 27	ENST00000357701.6	NP_004524.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYBPC2	ENST00000357701.6	c.19+149C>T		intron_variant	Intron 1 of 27	1	NM_004533.4	ENSP00000350332.4

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56100 AN: 151818 Hom.: 11498 Cov.: 31

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.435

GnomAD4 exome AF: 0.408 AC: 341420 AN: 837500 Hom.: 73285 AF XY: 0.412 AC XY: 171976 AN XY: 417864

Gnomad4 AFR exome AF: 0.177

Gnomad4 AMR exome AF: 0.527

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.482

Gnomad4 SAS exome AF: 0.515

Gnomad4 FIN exome AF: 0.411

Gnomad4 NFE exome AF: 0.396

Gnomad4 OTH exome AF: 0.416

GnomAD4 genome AF: 0.369 AC: 56127 AN: 151936 Hom.: 11510 Cov.: 31 AF XY: 0.375 AC XY: 27854 AN XY: 74254

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.436

Alfa AF: 0.263 Hom.: 694

Bravo AF: 0.368

Asia WGS AF: 0.519 AC: 1805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3765069; hg19: chr19-50936378; COSMIC: COSV54531114; COSMIC: COSV54531114;