12-101614325-T-A

Position:

• chr12-101614325-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002465.4(MYBPC1):​c.26-171T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 139,794 control chromosomes in the GnomAD database, including 10,367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.39 (10367 hom., cov: 26)
• Consequence: MYBPC1 NM_002465.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.22

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]

LOC105369938 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 12-101614325-T-A is Benign according to our data. Variant chr12-101614325-T-A is described in ClinVar as [Benign]. Clinvar id is 1253396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBPC1	NM_002465.4	c.26-171T>A		intron_variant		ENST00000361466.7
LOC105369938	XR_001749279.2	n.722+229A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBPC1	ENST00000361466.7	c.26-171T>A		intron_variant		1	NM_002465.4	A2

Frequencies

GnomAD3 genomes AF: 0.386 AC: 53973 AN: 139738 Hom.: 10357 Cov.: 26

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.388

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.386 AC: 54017 AN: 139794 Hom.: 10367 Cov.: 26 AF XY: 0.385 AC XY: 26089 AN XY: 67724

Gnomad4 AFR AF: 0.547

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.386

Alfa AF: 0.148 Hom.: 217

Bravo AF: 0.375

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	clinical testing	GeneDx	Sep 04, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.12
DANN	Benign	0.87

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

Other links and lift over

dbSNP: rs825079; hg19: chr12-102008103;