10-88936457-T-G

Position:

• chr10-88936457-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001613.4(ACTA2):​c.991-1091A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 151,960 control chromosomes in the GnomAD database, including 26,064 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 0.58 (26064 hom., cov: 31)
• Consequence: ACTA2 NM_001613.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.217

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTA2	NM_001613.4	c.991-1091A>C		intron_variant		ENST00000224784.10	NP_001604.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTA2	ENST00000224784.10	c.991-1091A>C		intron_variant		1	NM_001613.4	ENSP00000224784.6

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87498 AN: 151842 Hom.: 26015 Cov.: 31

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.897

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.576 AC: 87603 AN: 151960 Hom.: 26064 Cov.: 31 AF XY: 0.581 AC XY: 43122 AN XY: 74268

Gnomad4 AFR AF: 0.639

Gnomad4 AMR AF: 0.673

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.898

Gnomad4 SAS AF: 0.769

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.500

Gnomad4 OTH AF: 0.601

Alfa AF: 0.536 Hom.: 2782

Bravo AF: 0.595

Asia WGS AF: 0.809 AC: 2812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.2
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs2028493; hg19: chr10-90696214;