12-101617224-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS1

The ENST00000551300(MYBPC1):​c.-289C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000367 in 1,613,654 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

MYBPC1
ENST00000551300 5_prime_UTR_premature_start_codon_gain

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.77
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
Variant 12-101617224-C-T is Benign according to our data. Variant chr12-101617224-C-T is described in ClinVar as [Benign]. Clinvar id is 723202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00191 (291/152158) while in subpopulation AFR AF= 0.00643 (267/41498). AF 95% confidence interval is 0.0058. There are 1 homozygotes in gnomad4. There are 139 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYBPC1NM_002465.4 linkc.84C>T p.Ala28Ala synonymous_variant Exon 3 of 32 ENST00000361466.7 NP_002456.2 Q00872-4Q86TA8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYBPC1ENST00000551300 linkc.-289C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 4 of 32 1 ENSP00000447116.1 G3V1V7
MYBPC1ENST00000361466.7 linkc.84C>T p.Ala28Ala synonymous_variant Exon 3 of 32 1 NM_002465.4 ENSP00000354849.2 Q00872-4
MYBPC1ENST00000551300 linkc.-289C>T 5_prime_UTR_variant Exon 4 of 32 1 ENSP00000447116.1 G3V1V7

Frequencies

GnomAD3 genomes
AF:
0.00191
AC:
291
AN:
152040
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00645
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00111
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000944
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.000526
AC:
132
AN:
251026
Hom.:
0
AF XY:
0.000509
AC XY:
69
AN XY:
135674
show subpopulations
Gnomad AFR exome
AF:
0.00647
Gnomad AMR exome
AF:
0.000609
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.000206
AC:
301
AN:
1461496
Hom.:
1
Cov.:
30
AF XY:
0.000188
AC XY:
137
AN XY:
727042
show subpopulations
Gnomad4 AFR exome
AF:
0.00670
Gnomad4 AMR exome
AF:
0.000672
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.00000809
Gnomad4 OTH exome
AF:
0.000613
GnomAD4 genome
AF:
0.00191
AC:
291
AN:
152158
Hom.:
1
Cov.:
32
AF XY:
0.00187
AC XY:
139
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.00643
Gnomad4 AMR
AF:
0.00111
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000944
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.00152
Hom.:
0
Bravo
AF:
0.00228
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Apr 18, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.35
CADD
Benign
4.4
DANN
Benign
0.67

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs74843538; hg19: chr12-102011002; API