Variant 15-34792014-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005159.5(ACTC1):c.808+76G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,525,606 control chromosomes in the GnomAD database, including 58,871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5161 hom., cov: 33)

Exomes 𝑓: 0.28 ( 53710 hom. )

Consequence

ACTC1
NM_005159.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.702

Variant links:

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]

ACTC1 links:

GJD2-DT (HGNC:55560): (GJD2 divergent transcript)

GJD2-DT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 15-34792014-C-G is Benign according to our data. Variant chr15-34792014-C-G is described in ClinVar as [Benign]. Clinvar id is 1292062.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-34792014-C-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTC1	NM_005159.5 linkuse as main transcript	c.808+76G>C		intron_variant		ENST00000290378.6	NP_005150.1
GJD2-DT	NR_120329.1 linkuse as main transcript	n.299+14583C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTC1	ENST00000290378.6 linkuse as main transcript	c.808+76G>C		intron_variant		1	NM_005159.5	ENSP00000290378	P1
GJD2-DT	ENST00000671663.1 linkuse as main transcript	n.95-18482C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38489

AN:

152018

Hom.:

5158

Cov.:

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.460

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.342

Gnomad SAS

AF:

0.335

Gnomad FIN

AF:

0.252

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.259

GnomAD4 exome

AF:

0.276

AC:

379105

AN:

1373470

Hom.:

53710

Cov.:

AF XY:

0.278

AC XY:

190899

AN XY:

686918

show subpopulations

Gnomad4 AFR exome

AF:

0.159

Gnomad4 AMR exome

AF:

0.376

Gnomad4 ASJ exome

AF:

0.259

Gnomad4 EAS exome

AF:

0.360

Gnomad4 SAS exome

AF:

0.334

Gnomad4 FIN exome

AF:

0.250

Gnomad4 NFE exome

AF:

0.270

Gnomad4 OTH exome

AF:

0.265

GnomAD4 genome

AF:

0.253

AC:

38496

AN:

152136

Hom.:

5161

Cov.:

AF XY:

0.255

AC XY:

18940

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.164

Gnomad4 AMR

AF:

0.345

Gnomad4 ASJ

AF:

0.256

Gnomad4 EAS

AF:

0.342

Gnomad4 SAS

AF:

0.334

Gnomad4 FIN

AF:

0.252

Gnomad4 NFE

AF:

0.271

Gnomad4 OTH

AF:

0.259

Alfa

AF:

0.249

Hom.:

604

Bravo

AF:

0.255

Asia WGS

AF:

0.334

AC:

1160

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
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

-0.84

CADD

Benign

1.8

DANN

Benign

0.56

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over