rs952061

Variant names:

• chr12-101584447-C-T
• rs952061
• ENST00000550514.5:c.-195+15942C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

MYBPC1 Gene-Disease associations (from GenCC):

• arthrogryposis, distal, type 1B

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• myopathy, congenital, with tremor

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• lethal congenital contracture syndrome 4

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• digitotalar dysmorphism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• lethal congenital contracture syndrome 3

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYBPC1	ENST00000550514.5	c.-195+15942C>T		intron_variant	Intron 1 of 6	5		ENSP00000447404.1

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

African (AFR) AF: 0.0848 AC: 3513 AN: 41450

American (AMR) AF: 0.109 AC: 1661 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 751 AN: 3468

East Asian (EAS) AF: 0.0705 AC: 363 AN: 5152

South Asian (SAS) AF: 0.0811 AC: 390 AN: 4806

European-Finnish (FIN) AF: 0.157 AC: 1660 AN: 10564

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9204 AN: 67958

Other (OTH) AF: 0.137 AC: 289 AN: 2106

Alfa AF: 0.128 Hom.: 3134

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
PhyloP100		0.057

Splicing

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

Other links and lift over

dbSNP: rs952061; hg19: chr12-101978225;