10-88941888-A-T

Variant names:

• chr10-88941888-A-T
• rs714887
• NM_001613.4:c.370-19T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001613.4(ACTA2):​c.370-19T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,296 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ACTA2 NM_001613.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.729
• Publications: 0 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001613.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTA2	NM_001613.4	MANE Select	c.370-19T>A		intron	N/A	NP_001604.1	P62736
	ACTA2	NM_001141945.3		c.370-19T>A		intron	N/A	NP_001135417.1	D2JYH4
	ACTA2	NM_001320855.2		c.370-19T>A		intron	N/A	NP_001307784.1	P62736

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTA2	ENST00000224784.10	TSL:1 MANE Select	c.370-19T>A		intron	N/A	ENSP00000224784.6	P62736
	ACTA2	ENST00000713598.1		c.393T>A	p.Ala131Ala	synonymous	Exon 5 of 9	ENSP00000518894.1	A0AAQ5BGG5
	STAMBPL1	ENST00000371927.7	TSL:2	c.1254+19452A>T		intron	N/A	ENSP00000360995.3	Q96FJ0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449296 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 720030

African (AFR) AF: 0.00 AC: 0 AN: 33264

American (AMR) AF: 0.00 AC: 0 AN: 43322

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25866

East Asian (EAS) AF: 0.00 AC: 0 AN: 39252

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52694

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104630

Other (OTH) AF: 0.00 AC: 0 AN: 59938

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs714887; hg19: chr10-90701645;