15-34793000-C-T

Position:

• chr15-34793000-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005159.5(ACTC1):​c.454+245G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 568,658 control chromosomes in the GnomAD database, including 101,963 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (29715 hom., cov: 32)
  • Exomes 𝑓: 0.59 (72248 hom.)
• Consequence: ACTC1 NM_005159.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.56

Genes affected

ACTC1 (HGNC:143): (actin alpha cardiac muscle 1) Actins are highly conserved proteins that are involved in various types of cell motility. Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to four others. The protein encoded by this gene belongs to the actin family which is comprised of three main groups of actin isoforms, alpha, beta, and gamma. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. Defects in this gene have been associated with idiopathic dilated cardiomyopathy (IDC) and familial hypertrophic cardiomyopathy (FHC). [provided by RefSeq, Jul 2008]

GJD2-DT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 15-34793000-C-T is Benign according to our data. Variant chr15-34793000-C-T is described in ClinVar as [Benign]. Clinvar id is 677956.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTC1	NM_005159.5	c.454+245G>A		intron_variant		ENST00000290378.6	NP_005150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTC1	ENST00000290378.6	c.454+245G>A		intron_variant		1	NM_005159.5	ENSP00000290378.4

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94392 AN: 151846 Hom.: 29659 Cov.: 32

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.611

GnomAD4 exome AF: 0.586 AC: 244365 AN: 416694 Hom.: 72248 AF XY: 0.589 AC XY: 129414 AN XY: 219844

Gnomad4 AFR exome AF: 0.715

Gnomad4 AMR exome AF: 0.603

Gnomad4 ASJ exome AF: 0.535

Gnomad4 EAS exome AF: 0.547

Gnomad4 SAS exome AF: 0.632

Gnomad4 FIN exome AF: 0.502

Gnomad4 NFE exome AF: 0.588

Gnomad4 OTH exome AF: 0.584

GnomAD4 genome AF: 0.622 AC: 94496 AN: 151964 Hom.: 29715 Cov.: 32 AF XY: 0.617 AC XY: 45834 AN XY: 74274

Gnomad4 AFR AF: 0.722

Gnomad4 AMR AF: 0.615

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.635

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.616

Alfa AF: 0.593 Hom.: 26258

Bravo AF: 0.631

Asia WGS AF: 0.597 AC: 2073 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.0090
DANN	Benign	0.66

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: rs2070664; hg19: chr15-35085201;