chr12-101675299-A-G

Position:

chr12-101675299-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002465.4(MYBPC1):c.2817A>G(p.Pro939=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,613,562 control chromosomes in the GnomAD database, including 57,662 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3755 hom., cov: 32)

Exomes 𝑓: 0.26 ( 53907 hom. )

Consequence

MYBPC1
NM_002465.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.05

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 12-101675299-A-G is Benign according to our data. Variant chr12-101675299-A-G is described in ClinVar as [Benign]. Clinvar id is 129645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101675299-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.05 with no splicing effect.

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 linkuse as main transcript	c.2817A>G	p.Pro939=	synonymous_variant	26/32	ENST00000361466.7	NP_002456.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYBPC1	ENST00000361466.7 linkuse as main transcript	c.2817A>G	p.Pro939=	synonymous_variant	26/32	1	NM_002465.4	ENSP00000354849	A2	Q00872-4

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

31184

AN:

152096

Hom.:

3757

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0767

Gnomad AMI

AF:

0.191

Gnomad AMR

AF:

0.182

Gnomad ASJ

AF:

0.304

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.266

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.279

Gnomad OTH

AF:

0.215

GnomAD3 exomes

AF:

0.223

AC:

55979

AN:

250936

Hom.:

7089

AF XY:

0.231

AC XY:

31339

AN XY:

135588

show subpopulations

Gnomad AFR exome

AF:

0.0705

Gnomad AMR exome

AF:

0.137

Gnomad ASJ exome

AF:

0.302

Gnomad EAS exome

AF:

0.0861

Gnomad SAS exome

AF:

0.227

Gnomad FIN exome

AF:

0.264

Gnomad NFE exome

AF:

0.276

Gnomad OTH exome

AF:

0.249

GnomAD4 exome

AF:

0.265

AC:

387138

AN:

1461346

Hom.:

53907

Cov.:

AF XY:

0.265

AC XY:

192720

AN XY:

726966

show subpopulations

Gnomad4 AFR exome

AF:

0.0727

Gnomad4 AMR exome

AF:

0.142

Gnomad4 ASJ exome

AF:

0.302

Gnomad4 EAS exome

AF:

0.0893

Gnomad4 SAS exome

AF:

0.230

Gnomad4 FIN exome

AF:

0.263

Gnomad4 NFE exome

AF:

0.284

Gnomad4 OTH exome

AF:

0.257

GnomAD4 genome

AF:

0.205

AC:

31177

AN:

152216

Hom.:

3755

Cov.:

AF XY:

0.203

AC XY:

15080

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0766

Gnomad4 AMR

AF:

0.182

Gnomad4 ASJ

AF:

0.304

Gnomad4 EAS

AF:

0.111

Gnomad4 SAS

AF:

0.225

Gnomad4 FIN

AF:

0.266

Gnomad4 NFE

AF:

0.279

Gnomad4 OTH

AF:

0.216

Alfa

AF:

0.259

Hom.:

10240

Bravo

AF:

0.189

Asia WGS

AF:

0.152

AC:

531

AN:

3478

EpiCase

AF:

0.278

EpiControl

AF:

0.273

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Arthrogryposis, distal, type 1B

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

Myopathy, congenital, with tremor

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Lethal congenital contracture syndrome 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

3.3

DANN

Benign

0.59

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over