chr10-88989499-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001141945.3(ACTA2):c.-24+1440C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 543,676 control chromosomes in the GnomAD database, including 6,468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.11 ( 1426 hom., cov: 32)

Exomes 𝑓: 0.14 ( 5042 hom. )

Consequence

ACTA2
NM_001141945.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: -0.866

Variant links:

Genes affected

FAS (HGNC:11920): (Fas cell surface death receptor) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contains a death domain. It has been shown to play a central role in the physiological regulation of programmed cell death, and has been implicated in the pathogenesis of various malignancies and diseases of the immune system. The interaction of this receptor with its ligand allows the formation of a death-inducing signaling complex that includes Fas-associated death domain protein (FADD), caspase 8, and caspase 10. The autoproteolytic processing of the caspases in the complex triggers a downstream caspase cascade, and leads to apoptosis. This receptor has been also shown to activate NF-kappaB, MAPK3/ERK1, and MAPK8/JNK, and is found to be involved in transducing the proliferating signals in normal diploid fibroblast and T cells. Several alternatively spliced transcript variants have been described, some of which are candidates for nonsense-mediated mRNA decay (NMD). The isoforms lacking the transmembrane domain may negatively regulate the apoptosis mediated by the full length isoform. [provided by RefSeq, Mar 2011]

FAS links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 10-88989499-G-A is Benign according to our data. Variant chr10-88989499-G-A is described in ClinVar as [Benign]. Clinvar id is 16517.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
FAS	XM_011539764.3 link	c.112G>A	p.Ala38Thr	missense_variant	Exon 2 of 10	XP_011538066.1
FAS	XM_011539765.3 link	c.112G>A	p.Ala38Thr	missense_variant	Exon 2 of 9	XP_011538067.1
FAS	XM_006717819.4 link	c.31G>A	p.Ala11Thr	missense_variant	Exon 2 of 10	XP_006717882.1	Q59FU8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
FAS	ENST00000690268.1 link	c.31G>A	p.Ala11Thr	missense_variant	Exon 3 of 11		ENSP00000509810.1	Q59FU8
ACTA2	ENST00000415557.2 link	c.-24+1440C>T		intron_variant	Intron 1 of 8	3	ENSP00000396730.2	F6QUT6
ACTA2	ENST00000458159.6 link	c.-24+1523C>T		intron_variant	Intron 1 of 8	3	ENSP00000398239.2	F6UVQ4

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17311

AN:

151962

Hom.:

1428

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0470

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.163

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.420

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.121

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.113

Gnomad OTH

AF:

0.129

GnomAD3 exomes

AF:

0.151

AC:

34536

AN:

229260

Hom.:

3511

AF XY:

0.149

AC XY:

18932

AN XY:

126712

show subpopulations

Gnomad AFR exome

AF:

0.0447

Gnomad AMR exome

AF:

0.172

Gnomad ASJ exome

AF:

0.114

Gnomad EAS exome

AF:

0.425

Gnomad SAS exome

AF:

0.176

Gnomad FIN exome

AF:

0.120

Gnomad NFE exome

AF:

0.112

Gnomad OTH exome

AF:

0.139

GnomAD4 exome

AF:

0.141

AC:

55307

AN:

391596

Hom.:

5042

Cov.:

AF XY:

0.142

AC XY:

31435

AN XY:

221656

show subpopulations

Gnomad4 AFR exome

AF:

0.0480

Gnomad4 AMR exome

AF:

0.171

Gnomad4 ASJ exome

AF:

0.118

Gnomad4 EAS exome

AF:

0.423

Gnomad4 SAS exome

AF:

0.171

Gnomad4 FIN exome

AF:

0.116

Gnomad4 NFE exome

AF:

0.111

Gnomad4 OTH exome

AF:

0.135

GnomAD4 genome

AF:

0.114

AC:

17313

AN:

152080

Hom.:

1426

Cov.:

AF XY:

0.118

AC XY:

8766

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0470

Gnomad4 AMR

AF:

0.163

Gnomad4 ASJ

AF:

0.123

Gnomad4 EAS

AF:

0.420

Gnomad4 SAS

AF:

0.187

Gnomad4 FIN

AF:

0.121

Gnomad4 NFE

AF:

0.113

Gnomad4 OTH

AF:

0.130

Alfa

AF:

0.111

Hom.:

251

Bravo

AF:

0.112

Asia WGS

AF:

0.327

AC:

1135

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 33% of patients studied by a panel of primary immunodeficiencies. Number of patients: 31. Only high quality variants are reported. -

LUNG CANCER, SUSCEPTIBILITY TO

Other:1

Jun 01, 2005

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.31

DANN

Benign

0.50

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over