rs3781211

Variant names:

• chr10-88935508-G-T
• rs3781211
• NM_001613.4:c.991-142C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.725

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]

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]

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ACTA2	NM_001613.4	c.991-142C>A		intron_variant	Intron 8 of 8	ENST00000224784.10	NP_001604.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTA2	ENST00000224784.10	c.991-142C>A		intron_variant	Intron 8 of 8	1	NM_001613.4	ENSP00000224784.6

Frequencies

GnomAD3 genomes AF: 0.0968 AC: 14717 AN: 152094 Hom.: 928 Cov.: 32

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.: 10 AF XY: 0.122 AC XY: 48337 AN XY: 395126

African (AFR) AF: 0.0793 AC: 1594 AN: 20096

American (AMR) AF: 0.115 AC: 4107 AN: 35722

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 2679 AN: 20000

East Asian (EAS) AF: 0.250 AC: 8345 AN: 33332

South Asian (SAS) AF: 0.331 AC: 22228 AN: 67242

European-Finnish (FIN) AF: 0.0594 AC: 2156 AN: 36306

Middle Eastern (MID) AF: 0.154 AC: 655 AN: 4266

European-Non Finnish (NFE) AF: 0.0777 AC: 39248 AN: 505244

Other (OTH) AF: 0.118 AC: 4347 AN: 36818

GnomAD4 genome AF: 0.0967 AC: 14726 AN: 152212 Hom.: 930 Cov.: 32 AF XY: 0.103 AC XY: 7646 AN XY: 74402

African (AFR) AF: 0.0771 AC: 3201 AN: 41542

American (AMR) AF: 0.119 AC: 1826 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 443 AN: 3472

East Asian (EAS) AF: 0.268 AC: 1383 AN: 5170

South Asian (SAS) AF: 0.343 AC: 1656 AN: 4822

European-Finnish (FIN) AF: 0.0532 AC: 564 AN: 10600

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.0779 AC: 5300 AN: 68000

Other (OTH) AF: 0.118 AC: 248 AN: 2110

Alfa AF: 0.0853 Hom.: 101

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

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.80
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

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

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Other links and lift over

dbSNP: rs3781211; hg19: chr10-90695265; COSMIC: COSV56515949; COSMIC: COSV56515949;