10-88990206-A-G

Variant names:

• chr10-88990206-A-G
• rs1800682
• ENST00000651408.1:n.4044T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000651408.1(ENSG00000286116):​n.4044T>C 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 0.536 in 152,064 control chromosomes in the GnomAD database, including 22,963 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.54 (22963 hom., cov: 32)
• Consequence: ENSG00000286116 ENST00000651408.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0250
• Publications: 351 publications found

Genes affected

ENSG00000286116 (HGNC:):

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]

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 Gene-Disease associations (from GenCC):

• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• multisystemic smooth muscle dysfunction syndrome

  Inheritance: AD, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• aortic aneurysm, familial thoracic 6

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
• Moyamoya disease 5

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, G2P
• connective tissue disorder

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-88990206-A-G is Benign according to our data. Variant chr10-88990206-A-G is described in ClinVar as Benign. ClinVar VariationId is 779595.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTA2	NM_001141945.3	c.-24+733T>C		intron_variant	Intron 1 of 8		NP_001135417.1
ACTA2	NM_001320855.2	c.-24+816T>C		intron_variant	Intron 1 of 8		NP_001307784.1
ACTA2	NM_001406462.1	c.-182+816T>C		intron_variant	Intron 1 of 9		NP_001393391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000286116	ENST00000651408.1	n.4044T>C		non_coding_transcript_exon_variant	Exon 1 of 1
FAS	ENST00000688239.1	n.372A>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 4 of 4
ACTA2	ENST00000415557.2	c.-24+733T>C		intron_variant	Intron 1 of 8	3		ENSP00000396730.2

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81399 AN: 151942 Hom.: 22905 Cov.: 32

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.513

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

GnomAD4 genome AF: 0.536 AC: 81523 AN: 152064 Hom.: 22963 Cov.: 32 AF XY: 0.535 AC XY: 39759 AN XY: 74334

African (AFR) AF: 0.721 AC: 29904 AN: 41470

American (AMR) AF: 0.531 AC: 8119 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1425 AN: 3468

East Asian (EAS) AF: 0.472 AC: 2439 AN: 5166

South Asian (SAS) AF: 0.434 AC: 2092 AN: 4820

European-Finnish (FIN) AF: 0.450 AC: 4761 AN: 10580

Middle Eastern (MID) AF: 0.490 AC: 142 AN: 290

European-Non Finnish (NFE) AF: 0.458 AC: 31118 AN: 67964

Other (OTH) AF: 0.516 AC: 1087 AN: 2106

Alfa AF: 0.487 Hom.: 78067

Bravo AF: 0.550

Asia WGS AF: 0.533 AC: 1854 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autoimmune lymphoproliferative syndrome type 1 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.1
DANN	Benign	0.54
PhyloP100		-0.025
PromoterAI		0.062	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1800682; hg19: chr10-90749963;