10-89023563-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000690268.1(FAS):c.*9113C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 151,988 control chromosomes in the GnomAD database, including 28,695 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 0.61 (28695 hom., cov: 32)
• Consequence: FAS ENST00000690268.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAS	ENST00000690268.1	c.*9113C>T		3_prime_UTR_variant	11/11			A2

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92320 AN: 151870 Hom.: 28664 Cov.: 32

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.623

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

GnomAD4 genome AF: 0.608 AC: 92410 AN: 151988 Hom.: 28695 Cov.: 32 AF XY: 0.617 AC XY: 45840 AN XY: 74288

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.686

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.965

Gnomad4 SAS AF: 0.688

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.620

Alfa AF: 0.565 Hom.: 16416

Bravo AF: 0.615

Asia WGS AF: 0.805 AC: 2800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.1
Dann	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4934436; hg19: chr10-90783320;