12-101594747-C-T

Position:

• chr12-101594747-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000550514.5(MYBPC1):​c.-195+26242C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 245,714 control chromosomes in the GnomAD database, including 17,295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9846 hom., cov: 32)
  • Exomes 𝑓: 0.39 (7449 hom.)
• Consequence: MYBPC1 ENST00000550514.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0360

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]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 12-101594747-C-T is Benign according to our data. Variant chr12-101594747-C-T is described in ClinVar as [Benign]. Clinvar id is 1296793.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBPC1	ENST00000550514.5	c.-195+26242C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53828 AN: 151738 Hom.: 9851 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.390

GnomAD4 exome AF: 0.390 AC: 36599 AN: 93856 Hom.: 7449 AF XY: 0.391 AC XY: 18647 AN XY: 47750

Gnomad4 AFR exome AF: 0.247

Gnomad4 AMR exome AF: 0.342

Gnomad4 ASJ exome AF: 0.452

Gnomad4 EAS exome AF: 0.476

Gnomad4 SAS exome AF: 0.387

Gnomad4 FIN exome AF: 0.391

Gnomad4 NFE exome AF: 0.386

Gnomad4 OTH exome AF: 0.390

GnomAD4 genome AF: 0.355 AC: 53845 AN: 151858 Hom.: 9846 Cov.: 32 AF XY: 0.356 AC XY: 26438 AN XY: 74174

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.391

Alfa AF: 0.379 Hom.: 15918

Bravo AF: 0.347

Asia WGS AF: 0.424 AC: 1474 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1405712; hg19: chr12-101988525;