Variant 12-101661139-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002465.4(MYBPC1):c.1928-19T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00567 in 1,569,988 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0059 ( 47 hom. )

Consequence

MYBPC1
NM_002465.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.414

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 12-101661139-T-G is Benign according to our data. Variant chr12-101661139-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 258661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0034 (518/152334) while in subpopulation SAS AF= 0.012 (58/4818). AF 95% confidence interval is 0.00956. There are 4 homozygotes in gnomad4. There are 257 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYBPC1	NM_002465.4 linkuse as main transcript	c.1928-19T>G		intron_variant		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.1928-19T>G		intron_variant		1	NM_002465.4	ENSP00000354849.2		Q00872-4
MYBPC1	ENST00000551300.5 linkuse as main transcript	c.1556-19T>G		intron_variant		1		ENSP00000447116.1		G3V1V7

Frequencies

GnomAD3 genomes

AF:

0.00340

AC:

517

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0118

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00520

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00450

AC:

1121

AN:

249276

Hom.:

AF XY:

0.00501

AC XY:

675

AN XY:

134674

show subpopulations

Gnomad AFR exome

AF:

0.000559

Gnomad AMR exome

AF:

0.00131

Gnomad ASJ exome

AF:

0.000896

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0141

Gnomad FIN exome

AF:

0.000371

Gnomad NFE exome

AF:

0.00532

Gnomad OTH exome

AF:

0.00393

GnomAD4 exome

AF:

0.00592

AC:

8386

AN:

1417654

Hom.:

Cov.:

AF XY:

0.00609

AC XY:

4314

AN XY:

707936

show subpopulations

Gnomad4 AFR exome

AF:

0.000614

Gnomad4 AMR exome

AF:

0.00124

Gnomad4 ASJ exome

AF:

0.00104

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0133

Gnomad4 FIN exome

AF:

0.000432

Gnomad4 NFE exome

AF:

0.00622

Gnomad4 OTH exome

AF:

0.00669

GnomAD4 genome

AF:

0.00340

AC:

518

AN:

152334

Hom.:

Cov.:

AF XY:

0.00345

AC XY:

257

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0120

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00520

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00259

Hom.:

Bravo

AF:

0.00333

Asia WGS

AF:

0.00577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 06, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.57

DANN

Benign

0.67

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