rs952061

Positions:

• chr12-101584447-C-T

Variant summary

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

The ENST00000550514.5(MYBPC1):​c.-195+15942C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 151,968 control chromosomes in the GnomAD database, including 1,177 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 0.12 (1177 hom., cov: 31)
• Consequence: MYBPC1 ENST00000550514.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

Genes affected

MYBPC1 (HGNC:7549): (myosin binding protein C1) This gene encodes a member of the myosin-binding protein C family. Myosin-binding protein C family members are myosin-associated proteins found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. The encoded protein is the slow skeletal muscle isoform of myosin-binding protein C and plays an important role in muscle contraction by recruiting muscle-type creatine kinase to myosin filaments. Mutations in this gene are associated with distal arthrogryposis type I. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBPC1	ENST00000550514.5	c.-195+15942C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18071 AN: 151850 Hom.: 1177 Cov.: 31

Gnomad AFR AF: 0.0847

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.0707

Gnomad SAS AF: 0.0807

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.119 AC: 18072 AN: 151968 Hom.: 1177 Cov.: 31 AF XY: 0.119 AC XY: 8851 AN XY: 74278

Gnomad4 AFR AF: 0.0848

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.0705

Gnomad4 SAS AF: 0.0811

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.137

Alfa AF: 0.130 Hom.: 1075

Bravo AF: 0.115

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs952061; hg19: chr12-101978225;