rs10405793

Positions:

• chr19-50445293-A-T

Variant summary

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

The NM_004533.4(MYBPC2):​c.1134-587A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 151,738 control chromosomes in the GnomAD database, including 11,887 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 0.39 (11887 hom., cov: 30)
• Consequence: MYBPC2 NM_004533.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBPC2	NM_004533.4	c.1134-587A>T		intron_variant		ENST00000357701.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBPC2	ENST00000357701.6	c.1134-587A>T		intron_variant		1	NM_004533.4	P1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59745 AN: 151622 Hom.: 11872 Cov.: 30

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.394 AC: 59813 AN: 151738 Hom.: 11887 Cov.: 30 AF XY: 0.391 AC XY: 28969 AN XY: 74114

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.400

Alfa AF: 0.393 Hom.: 1403

Bravo AF: 0.397

Asia WGS AF: 0.345 AC: 1198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.10
DANN	Benign	0.74

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: rs10405793; hg19: chr19-50948550;