12-101614438-AG-A

Position:

• chr12-101614438-AG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002465.4(MYBPC1):​c.26-57del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0177 in 1,601,492 control chromosomes in the GnomAD database, including 1,305 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.056 (644 hom., cov: 32)
  • Exomes 𝑓: 0.014 (661 hom.)
• Consequence: MYBPC1 NM_002465.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.17

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]

LOC105369938 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-101614438-AG-A is Benign according to our data. Variant chr12-101614438-AG-A is described in ClinVar as [Benign]. Clinvar id is 1278156.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYBPC1	NM_002465.4	c.26-57del		intron_variant		ENST00000361466.7	NP_002456.2
LOC105369938	XR_001749279.2	n.722+115del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYBPC1	ENST00000361466.7	c.26-57del		intron_variant		1	NM_002465.4	ENSP00000354849	A2

Frequencies

GnomAD3 genomes AF: 0.0562 AC: 8557 AN: 152128 Hom.: 643 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.0323

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00767

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.0445

GnomAD4 exome AF: 0.0137 AC: 19837 AN: 1449246 Hom.: 661 AF XY: 0.0131 AC XY: 9428 AN XY: 721588

Gnomad4 AFR exome AF: 0.174

Gnomad4 AMR exome AF: 0.0174

Gnomad4 ASJ exome AF: 0.00480

Gnomad4 EAS exome AF: 0.0000506

Gnomad4 SAS exome AF: 0.00764

Gnomad4 FIN exome AF: 0.00234

Gnomad4 NFE exome AF: 0.0100

Gnomad4 OTH exome AF: 0.0199

GnomAD4 genome AF: 0.0563 AC: 8572 AN: 152246 Hom.: 644 Cov.: 32 AF XY: 0.0544 AC XY: 4048 AN XY: 74450

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.0322

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00767

Gnomad4 FIN AF: 0.00160

Gnomad4 NFE AF: 0.0102

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.00366 Hom.: 4

Bravo AF: 0.0642

Asia WGS AF: 0.0140 AC: 48 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 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs111379309; hg19: chr12-102008216;