rs11110932

Positions:

• chr12-101656397-G-A

Variant summary

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

The NM_002465.4(MYBPC1):​c.1767+3149G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 151,948 control chromosomes in the GnomAD database, including 4,085 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 0.22 (4085 hom., cov: 32)
• Consequence: MYBPC1 NM_002465.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.329

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]

ENSG00000257514 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYBPC1	NM_002465.4	c.1767+3149G>A		intron_variant		ENST00000361466.7	NP_002456.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYBPC1	ENST00000361466.7	c.1767+3149G>A		intron_variant		1	NM_002465.4	ENSP00000354849.2
MYBPC1	ENST00000551300.5	c.1395+3149G>A		intron_variant		1		ENSP00000447116.1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34074 AN: 151828 Hom.: 4087 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.224 AC: 34070 AN: 151948 Hom.: 4085 Cov.: 32 AF XY: 0.222 AC XY: 16483 AN XY: 74262

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.230

Alfa AF: 0.257 Hom.: 2630

Bravo AF: 0.211

Asia WGS AF: 0.155 AC: 538 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.7
DANN	Benign	0.49

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: rs11110932; hg19: chr12-102050175;