rs714887

Variant names:

Variant summary

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

The NM_001613.4(ACTA2):c.370-19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0874 in 1,601,224 control chromosomes in the GnomAD database, including 8,887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.089 ( 765 hom., cov: 32)

Exomes 𝑓: 0.087 ( 8122 hom. )

Consequence

ACTA2
NM_001613.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.729

Variant links:

Genes affected

ACTA2 (HGNC:130): (actin alpha 2, smooth muscle) This gene encodes one of six different actin proteins. Actins are highly conserved proteins that are involved in cell motility, structure, integrity, and intercellular signaling. The encoded protein is a smooth muscle actin that is involved in vascular contractility and blood pressure homeostasis. Mutations in this gene cause a variety of vascular diseases, such as thoracic aortic disease, coronary artery disease, stroke, and Moyamoya disease, as well as multisystemic smooth muscle dysfunction syndrome. [provided by RefSeq, Sep 2017]

ACTA2 links:

STAMBPL1 (HGNC:24105): (STAM binding protein like 1) Predicted to enable Lys63-specific deubiquitinase activity and thiol-dependent deubiquitinase. Predicted to be involved in protein K63-linked deubiquitination. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

STAMBPL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 10-88941888-A-G is Benign according to our data. Variant chr10-88941888-A-G is described in ClinVar as [Benign]. Clinvar id is 136279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-88941888-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTA2	NM_001613.4 link	c.370-19T>C		intron_variant	Intron 4 of 8	ENST00000224784.10	NP_001604.1	P62736D2JYH4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTA2	ENST00000224784.10 link	c.370-19T>C		intron_variant	Intron 4 of 8	1	NM_001613.4	ENSP00000224784.6		P62736

Frequencies

GnomAD3 genomes

AF:

0.0887

AC:

13497

AN:

152096

Hom.:

762

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0767

Gnomad AMI

AF:

0.00879

Gnomad AMR

AF:

0.111

Gnomad ASJ

AF:

0.135

Gnomad EAS

AF:

0.267

Gnomad SAS

AF:

0.281

Gnomad FIN

AF:

0.0455

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.0681

Gnomad OTH

AF:

0.110

GnomAD3 exomes

AF:

0.120

AC:

27865

AN:

231922

Hom.:

2434

AF XY:

0.127

AC XY:

15802

AN XY:

124906

show subpopulations

Gnomad AFR exome

AF:

0.0786

Gnomad AMR exome

AF:

0.114

Gnomad ASJ exome

AF:

0.140

Gnomad EAS exome

AF:

0.278

Gnomad SAS exome

AF:

0.281

Gnomad FIN exome

AF:

0.0529

Gnomad NFE exome

AF:

0.0692

Gnomad OTH exome

AF:

0.109

GnomAD4 exome

AF:

0.0872

AC:

126402

AN:

1449010

Hom.:

8122

Cov.:

AF XY:

0.0926

AC XY:

66633

AN XY:

719880

show subpopulations

Gnomad4 AFR exome

AF:

0.0769

Gnomad4 AMR exome

AF:

0.114

Gnomad4 ASJ exome

AF:

0.144

Gnomad4 EAS exome

AF:

0.255

Gnomad4 SAS exome

AF:

0.272

Gnomad4 FIN exome

AF:

0.0532

Gnomad4 NFE exome

AF:

0.0654

Gnomad4 OTH exome

AF:

0.107

GnomAD4 genome

AF:

0.0887

AC:

13505

AN:

152214

Hom.:

765

Cov.:

AF XY:

0.0940

AC XY:

6997

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0768

Gnomad4 AMR

AF:

0.111

Gnomad4 ASJ

AF:

0.135

Gnomad4 EAS

AF:

0.267

Gnomad4 SAS

AF:

0.281

Gnomad4 FIN

AF:

0.0455

Gnomad4 NFE

AF:

0.0681

Gnomad4 OTH

AF:

0.113

Alfa

AF:

0.0821

Hom.:

123

Bravo

AF:

0.0891

Asia WGS

AF:

0.273

AC:

949

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 06, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aortic aneurysm, familial thoracic 6

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Thoracic aortic aneurysm

Benign:1

Sep 23, 2022

Cohesion Phenomics

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.84

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