Variant rs3781211 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_001613.4(ACTA2):c.991-142C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 911,238 control chromosomes in the GnomAD database, including 8,312 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.097 ( 930 hom., cov: 32)

Exomes 𝑓: 0.11 ( 7382 hom. )

Consequence

ACTA2
NM_001613.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.725

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:

ACTA2-AS1 (HGNC:45169): (ACTA2 antisense RNA 1)

ACTA2-AS1 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=-0.83).

BP6

Variant 10-88935508-G-T is Benign according to our data. Variant chr10-88935508-G-T is described in ClinVar as [Benign]. Clinvar id is 1229059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTA2	NM_001613.4 link	c.991-142C>A		intron_variant		ENST00000224784.10	NP_001604.1	P62736D2JYH4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTA2	ENST00000224784.10 link	c.991-142C>A		intron_variant		1	NM_001613.4	ENSP00000224784.6		P62736

Frequencies

GnomAD3 genomes

AF:

0.0968

AC:

14717

AN:

152094

Hom.:

928

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0770

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.268

Gnomad SAS

AF:

0.343

Gnomad FIN

AF:

0.0532

Gnomad MID

AF:

0.191

Gnomad NFE

AF:

0.0779

Gnomad OTH

AF:

0.115

GnomAD4 exome

AF:

0.112

AC:

85359

AN:

759026

Hom.:

7382

Cov.:

AF XY:

0.122

AC XY:

48337

AN XY:

395126

show subpopulations

Gnomad4 AFR exome

AF:

0.0793

Gnomad4 AMR exome

AF:

0.115

Gnomad4 ASJ exome

AF:

0.134

Gnomad4 EAS exome

AF:

0.250

Gnomad4 SAS exome

AF:

0.331

Gnomad4 FIN exome

AF:

0.0594

Gnomad4 NFE exome

AF:

0.0777

Gnomad4 OTH exome

AF:

0.118

GnomAD4 genome

AF:

0.0967

AC:

14726

AN:

152212

Hom.:

930

Cov.:

AF XY:

0.103

AC XY:

7646

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0771

Gnomad4 AMR

AF:

0.119

Gnomad4 ASJ

AF:

0.128

Gnomad4 EAS

AF:

0.268

Gnomad4 SAS

AF:

0.343

Gnomad4 FIN

AF:

0.0532

Gnomad4 NFE

AF:

0.0779

Gnomad4 OTH

AF:

0.118

Alfa

AF:

0.0851

Hom.:

Bravo

AF:

0.0956

Asia WGS

AF:

0.288

AC:

999

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.8

DANN

Benign

0.80

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