10-88935036-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NR_125373.1(ACTA2-AS1):n.661G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 732,328 control chromosomes in the GnomAD database, including 529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.028 (127 hom., cov: 32)
  • Exomes 𝑓: 0.020 (402 hom.)
• Consequence: ACTA2-AS1 NR_125373.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.69

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 10-88935036-G-T is Benign according to our data. Variant chr10-88935036-G-T is described in ClinVar as [Benign]. Clinvar id is 1278133.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-88935036-G-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTA2-AS1	NR_125373.1	n.661G>T		non_coding_transcript_exon_variant	3/5
ACTA2	NM_001613.4			downstream_gene_variant		ENST00000224784.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTA2-AS1	ENST00000437930.4	n.702G>T		non_coding_transcript_exon_variant	3/5	2
STAMBPL1	ENST00000371927.7	c.1254+12600G>T		intron_variant		2
ACTA2	ENST00000224784.10			downstream_gene_variant		1	NM_001613.4	P1
ACTA2	ENST00000458159.6			downstream_gene_variant		3		P1

Frequencies

GnomAD3 genomes AF: 0.0275 AC: 4187 AN: 152046 Hom.: 127 Cov.: 32

Gnomad AFR AF: 0.0538

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00995

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.0422

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.00903

Gnomad OTH AF: 0.0268

GnomAD4 exome AF: 0.0198 AC: 11508 AN: 580164 Hom.: 402 Cov.: 8 AF XY: 0.0206 AC XY: 6244 AN XY: 303018

Gnomad4 AFR exome AF: 0.0533

Gnomad4 AMR exome AF: 0.00837

Gnomad4 ASJ exome AF: 0.0533

Gnomad4 EAS exome AF: 0.138

Gnomad4 SAS exome AF: 0.0349

Gnomad4 FIN exome AF: 0.00221

Gnomad4 NFE exome AF: 0.00843

Gnomad4 OTH exome AF: 0.0228

GnomAD4 genome AF: 0.0276 AC: 4205 AN: 152164 Hom.: 127 Cov.: 32 AF XY: 0.0280 AC XY: 2083 AN XY: 74390

Gnomad4 AFR AF: 0.0539

Gnomad4 AMR AF: 0.00987

Gnomad4 ASJ AF: 0.0568

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.0425

Gnomad4 FIN AF: 0.00198

Gnomad4 NFE AF: 0.00903

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0119 Hom.: 17

Bravo AF: 0.0297

Asia WGS AF: 0.0950 AC: 330 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.0090
Dann	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7908852; hg19: chr10-90694793;