12-101670340-T-C

Position:

chr12-101670340-T-C

Variant summary

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

The NM_002465.4(MYBPC1):c.2544T>C(p.Ile848Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.952 in 1,613,850 control chromosomes in the GnomAD database, including 731,518 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.95 ( 69053 hom., cov: 32)

Exomes 𝑓: 0.95 ( 662465 hom. )

Consequence

MYBPC1
NM_002465.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.458

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:

MYBPC1 (HGNC:):

MYBPC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 12-101670340-T-C is Benign according to our data. Variant chr12-101670340-T-C is described in ClinVar as [Benign]. Clinvar id is 129644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101670340-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.458 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.2544T>C	p.Ile848Ile	synonymous_variant	24/32	ENST00000361466.7	NP_002456.2	Q00872-4Q86TA8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYBPC1	ENST00000361466.7 linkuse as main transcript	c.2544T>C	p.Ile848Ile	synonymous_variant	24/32	1	NM_002465.4	ENSP00000354849.2		Q00872-4
MYBPC1	ENST00000551300.5 linkuse as main transcript	c.2172T>C	p.Ile724Ile	synonymous_variant	25/32	1		ENSP00000447116.1		G3V1V7

Frequencies

GnomAD3 genomes

AF:

0.952

AC:

144869

AN:

152166

Hom.:

69001

Cov.:

show subpopulations

Gnomad AFR

AF:

0.943

Gnomad AMI

AF:

0.831

Gnomad AMR

AF:

0.969

Gnomad ASJ

AF:

0.971

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.952

Gnomad FIN

AF:

0.956

Gnomad MID

AF:

0.981

Gnomad NFE

AF:

0.950

Gnomad OTH

AF:

0.955

GnomAD3 exomes

AF:

0.958

AC:

240827

AN:

251456

Hom.:

115369

AF XY:

0.956

AC XY:

129986

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.945

Gnomad AMR exome

AF:

0.977

Gnomad ASJ exome

AF:

0.974

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.953

Gnomad FIN exome

AF:

0.957

Gnomad NFE exome

AF:

0.947

Gnomad OTH exome

AF:

0.953

GnomAD4 exome

AF:

0.952

AC:

1391438

AN:

1461566

Hom.:

662465

Cov.:

AF XY:

0.952

AC XY:

692100

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.944

Gnomad4 AMR exome

AF:

0.975

Gnomad4 ASJ exome

AF:

0.971

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.953

Gnomad4 FIN exome

AF:

0.955

Gnomad4 NFE exome

AF:

0.949

Gnomad4 OTH exome

AF:

0.958

GnomAD4 genome

AF:

0.952

AC:

144980

AN:

152284

Hom.:

69053

Cov.:

AF XY:

0.953

AC XY:

70975

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.943

Gnomad4 AMR

AF:

0.970

Gnomad4 ASJ

AF:

0.971

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.952

Gnomad4 FIN

AF:

0.956

Gnomad4 NFE

AF:

0.950

Gnomad4 OTH

AF:

0.955

Alfa

AF:

0.952

Hom.:

36801

Bravo

AF:

0.953

Asia WGS

AF:

0.980

AC:

3410

AN:

3478

EpiCase

AF:

0.952

EpiControl

AF:

0.950

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

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+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

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 12, 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

-0.60

CADD

Benign

DANN

Benign

0.74

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