10-88937112-G-C

Position:

• chr10-88937112-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ACTA2	NM_001613.4	c.990+949C>G		intron_variant		ENST00000224784.10
ACTA2-AS1	NR_125373.1	n.1199-1100G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTA2	ENST00000224784.10	c.990+949C>G		intron_variant		1	NM_001613.4	P1
ACTA2-AS1	ENST00000437930.4	n.1240-1100G>C		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.627

Gnomad4 AMR AF: 0.667

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.886

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.588

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1441735; hg19: chr10-90696869;