chr12-101614487-C-T

Position:

chr12-101614487-C-T

Variant summary

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

The NM_002465.4(MYBPC1):c.26-9C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,613,710 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0093 ( 15 hom., cov: 32)

Exomes 𝑓: 0.012 ( 140 hom. )

Consequence

MYBPC1
NM_002465.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0002864

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.237

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:

LOC105369938 (HGNC:):

LOC105369938 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 12-101614487-C-T is Benign according to our data. Variant chr12-101614487-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 258662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101614487-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0093 (1417/152310) while in subpopulation NFE AF= 0.0123 (837/68022). AF 95% confidence interval is 0.0116. There are 15 homozygotes in gnomad4. There are 643 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYBPC1	NM_002465.4 linkuse as main transcript	c.26-9C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000361466.7	NP_002456.2
LOC105369938	XR_001749279.2 linkuse as main transcript	n.722+67G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYBPC1	ENST00000361466.7 linkuse as main transcript	c.26-9C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002465.4	ENSP00000354849	A2	Q00872-4

Frequencies

GnomAD3 genomes

AF:

0.00931

AC:

1417

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00282

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0117

Gnomad ASJ

AF:

0.0596

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0123

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.0102

AC:

2567

AN:

250704

Hom.:

AF XY:

0.0108

AC XY:

1462

AN XY:

135530

show subpopulations

Gnomad AFR exome

AF:

0.00241

Gnomad AMR exome

AF:

0.00945

Gnomad ASJ exome

AF:

0.0543

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00402

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.0127

Gnomad OTH exome

AF:

0.0149

GnomAD4 exome

AF:

0.0119

AC:

17356

AN:

1461400

Hom.:

140

Cov.:

AF XY:

0.0118

AC XY:

8589

AN XY:

727012

show subpopulations

Gnomad4 AFR exome

AF:

0.00379

Gnomad4 AMR exome

AF:

0.00956

Gnomad4 ASJ exome

AF:

0.0545

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00465

Gnomad4 FIN exome

AF:

0.000769

Gnomad4 NFE exome

AF:

0.0124

Gnomad4 OTH exome

AF:

0.0149

GnomAD4 genome

AF:

0.00930

AC:

1417

AN:

152310

Hom.:

Cov.:

AF XY:

0.00863

AC XY:

643

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00281

Gnomad4 AMR

AF:

0.0117

Gnomad4 ASJ

AF:

0.0596

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00539

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.0123

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.0134

Hom.:

Bravo

AF:

0.00977

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0148

EpiControl

AF:

0.0148

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	MYBPC1: BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 30, 2020	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Arthrogryposis, distal, type 1B

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00029

dbscSNV1_RF

Benign

0.010

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.20

Position offset: 44

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