12-101616962-A-C

Position:

• chr12-101616962-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002465.4(MYBPC1):​c.62-240A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,156 control chromosomes in the GnomAD database, including 1,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (1903 hom., cov: 32)
• Consequence: MYBPC1 NM_002465.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.233

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-101616962-A-C is Benign according to our data. Variant chr12-101616962-A-C is described in ClinVar as [Benign]. Clinvar id is 1181203.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBPC1	NM_002465.4	c.62-240A>C		intron_variant		ENST00000361466.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBPC1	ENST00000361466.7	c.62-240A>C		intron_variant		1	NM_002465.4	A2

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22156 AN: 152038 Hom.: 1900 Cov.: 32

Gnomad AFR AF: 0.0836

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.146 AC: 22171 AN: 152156 Hom.: 1903 Cov.: 32 AF XY: 0.144 AC XY: 10747 AN XY: 74392

Gnomad4 AFR AF: 0.0840

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.167

Alfa AF: 0.146 Hom.: 937

Bravo AF: 0.143

Asia WGS AF: 0.224 AC: 779 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	14
DANN	Benign	0.69

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: rs825087; hg19: chr12-102010740;