chr10-88937112-G-C

Variant names:

• chr10-88937112-G-C
• rs1441735
• NM_001613.4:c.990+949C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001613.4(ACTA2):​c.990+949C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 149,430 control chromosomes in the GnomAD database, including 24,326 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.57 (24326 hom., cov: 31)
• Consequence: ACTA2 NM_001613.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.619
• Publications: 3 publications found

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTA2	NM_001613.4	c.990+949C>G		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.990+949C>G		intron_variant	Intron 8 of 8	1	NM_001613.4	ENSP00000224784.6

Frequencies

GnomAD3 genomes AF: 0.565 AC: 84347 AN: 149312 Hom.: 24278 Cov.: 31

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.590

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.565 AC: 84451 AN: 149430 Hom.: 24326 Cov.: 31 AF XY: 0.569 AC XY: 41509 AN XY: 72968

African (AFR) AF: 0.627 AC: 25519 AN: 40710

American (AMR) AF: 0.667 AC: 10131 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 1974 AN: 3286

East Asian (EAS) AF: 0.886 AC: 4554 AN: 5140

South Asian (SAS) AF: 0.723 AC: 3311 AN: 4580

European-Finnish (FIN) AF: 0.414 AC: 4302 AN: 10396

Middle Eastern (MID) AF: 0.603 AC: 176 AN: 292

European-Non Finnish (NFE) AF: 0.491 AC: 32824 AN: 66842

Other (OTH) AF: 0.588 AC: 1233 AN: 2096

Alfa AF: 0.258 Hom.: 364

Bravo AF: 0.587

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.9
DANN	Benign	0.65
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1441735; hg19: chr10-90696869;