rs112788142

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002465.4(MYBPC1):​c.556+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00276 in 1,566,610 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 61 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 51 hom. )

Consequence

MYBPC1
NM_002465.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.701
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]

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=-0.83).
BP6
Variant 12-101632147-G-A is Benign according to our data. Variant chr12-101632147-G-A is described in ClinVar as [Benign]. Clinvar id is 306722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101632147-G-A is described in Lovd as [Benign].
BA1
GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0509 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYBPC1NM_002465.4 linkc.556+9G>A intron_variant Intron 8 of 31 ENST00000361466.7 NP_002456.2 Q00872-4Q86TA8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYBPC1ENST00000361466.7 linkc.556+9G>A intron_variant Intron 8 of 31 1 NM_002465.4 ENSP00000354849.2 Q00872-4
MYBPC1ENST00000551300.5 linkc.184+9G>A intron_variant Intron 9 of 31 1 ENSP00000447116.1 G3V1V7

Frequencies

GnomAD3 genomes
AF:
0.0142
AC:
2155
AN:
152166
Hom.:
59
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0494
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00438
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000294
Gnomad OTH
AF:
0.0100
GnomAD3 exomes
AF:
0.00387
AC:
973
AN:
251454
Hom.:
25
AF XY:
0.00274
AC XY:
372
AN XY:
135906
show subpopulations
Gnomad AFR exome
AF:
0.0516
Gnomad AMR exome
AF:
0.00321
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000791
Gnomad OTH exome
AF:
0.00196
GnomAD4 exome
AF:
0.00152
AC:
2149
AN:
1414326
Hom.:
51
Cov.:
26
AF XY:
0.00126
AC XY:
893
AN XY:
706236
show subpopulations
Gnomad4 AFR exome
AF:
0.0530
Gnomad4 AMR exome
AF:
0.00345
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000821
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000571
Gnomad4 OTH exome
AF:
0.00330
GnomAD4 genome
AF:
0.0143
AC:
2176
AN:
152284
Hom.:
61
Cov.:
32
AF XY:
0.0139
AC XY:
1032
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.0497
Gnomad4 AMR
AF:
0.00438
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000294
Gnomad4 OTH
AF:
0.00993
Alfa
AF:
0.00718
Hom.:
14
Bravo
AF:
0.0160
Asia WGS
AF:
0.00375
AC:
13
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:4
Jan 25, 2021
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Apr 13, 2017
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Arthrogryposis, distal, type 1B Benign:1
Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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
-0.83
CADD
Benign
0.59
DANN
Benign
0.65

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.

Other links and lift over

dbSNP: rs112788142; hg19: chr12-102025925; API