ENST00000492756.7:n.*1859A>G

Variant names:

• chr10-89015872-A-G
• rs2862833
• ENST00000492756.7:n.*1859A>G

Variant summary

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

The ENST00000492756.7(FAS):​n.*1859A>G 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 0.456 in 375,126 control chromosomes in the GnomAD database, including 39,554 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 0.45 (15243 hom., cov: 32)
  • Exomes 𝑓: 0.46 (24311 hom.)
• Consequence: FAS ENST00000492756.7 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.462
• Publications: 22 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAS	NM_000043.6	c.*1422A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000652046.1	NP_000034.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAS	ENST00000652046.1	c.*1422A>G		3_prime_UTR_variant	Exon 9 of 9		NM_000043.6	ENSP00000498466.1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 67970 AN: 151858 Hom.: 15233 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.467

GnomAD4 exome AF: 0.462 AC: 103089 AN: 223150 Hom.: 24311 Cov.: 0 AF XY: 0.468 AC XY: 54778 AN XY: 117144

African (AFR) AF: 0.421 AC: 3224 AN: 7652

American (AMR) AF: 0.534 AC: 5399 AN: 10116

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 4575 AN: 9142

East Asian (EAS) AF: 0.506 AC: 8804 AN: 17400

South Asian (SAS) AF: 0.522 AC: 14635 AN: 28036

European-Finnish (FIN) AF: 0.447 AC: 2079 AN: 4656

Middle Eastern (MID) AF: 0.498 AC: 502 AN: 1008

European-Non Finnish (NFE) AF: 0.438 AC: 57557 AN: 131542

Other (OTH) AF: 0.464 AC: 6314 AN: 13598

GnomAD4 genome AF: 0.447 AC: 68006 AN: 151976 Hom.: 15243 Cov.: 32 AF XY: 0.452 AC XY: 33577 AN XY: 74286

African (AFR) AF: 0.418 AC: 17314 AN: 41446

American (AMR) AF: 0.500 AC: 7641 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1753 AN: 3470

East Asian (EAS) AF: 0.521 AC: 2696 AN: 5170

South Asian (SAS) AF: 0.514 AC: 2478 AN: 4824

European-Finnish (FIN) AF: 0.448 AC: 4729 AN: 10546

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29881 AN: 67932

Other (OTH) AF: 0.464 AC: 979 AN: 2112

Alfa AF: 0.449 Hom.: 8732

Bravo AF: 0.455

Asia WGS AF: 0.462 AC: 1605 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.73
PhyloP100		0.46

Splicing

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

Other links and lift over

dbSNP: rs2862833; hg19: chr10-90775629;