chr10-89019340-G-A

Variant names:

• chr10-89019340-G-A
• rs7915235
• ENST00000690268.1:c.*4890G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000690268.1(FAS):​c.*4890G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,098 control chromosomes in the GnomAD database, including 2,614 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 0.17 (2614 hom., cov: 32)
• Consequence: FAS ENST00000690268.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.569
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• autoimmune lymphoproliferative syndrome

  Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• autoimmune lymphoproliferative syndrome type 1

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000690268.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAS	ENST00000690268.1		c.*4890G>A		3_prime_UTR	Exon 11 of 11	ENSP00000509810.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25412 AN: 151978 Hom.: 2601 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.167 AC: 25466 AN: 152098 Hom.: 2614 Cov.: 32 AF XY: 0.172 AC XY: 12774 AN XY: 74346

African (AFR) AF: 0.229 AC: 9505 AN: 41468

American (AMR) AF: 0.195 AC: 2976 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 363 AN: 3468

East Asian (EAS) AF: 0.444 AC: 2292 AN: 5166

South Asian (SAS) AF: 0.200 AC: 964 AN: 4816

European-Finnish (FIN) AF: 0.169 AC: 1785 AN: 10576

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7125 AN: 67990

Other (OTH) AF: 0.165 AC: 348 AN: 2114

Alfa AF: 0.140 Hom.: 290

Bravo AF: 0.167

Asia WGS AF: 0.348 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.59
PhyloP100		0.57

Splicing

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

Other links and lift over

dbSNP: rs7915235; hg19: chr10-90779097;