rs1571011

Variant names:

• chr10-88998030-A-C
• rs1571011
• NM_000043.6:c.31-4999A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-88998030-A-C
• chr10-88998030-A-T

Variant summary

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

The NM_000043.6(FAS):​c.31-4999A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,036 control chromosomes in the GnomAD database, including 12,311 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 0.40 (12311 hom., cov: 31)
• Consequence: FAS NM_000043.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.954
• Publications: 26 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 = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAS	NM_000043.6	c.31-4999A>C		intron_variant	Intron 1 of 8	ENST00000652046.1	NP_000034.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAS	ENST00000652046.1	c.31-4999A>C		intron_variant	Intron 1 of 8		NM_000043.6	ENSP00000498466.1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60575 AN: 151918 Hom.: 12314 Cov.: 31

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.398 AC: 60580 AN: 152036 Hom.: 12311 Cov.: 31 AF XY: 0.404 AC XY: 30056 AN XY: 74314

African (AFR) AF: 0.328 AC: 13625 AN: 41478

American (AMR) AF: 0.395 AC: 6038 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1659 AN: 3466

East Asian (EAS) AF: 0.510 AC: 2634 AN: 5164

South Asian (SAS) AF: 0.454 AC: 2185 AN: 4818

European-Finnish (FIN) AF: 0.474 AC: 5006 AN: 10558

Middle Eastern (MID) AF: 0.445 AC: 130 AN: 292

European-Non Finnish (NFE) AF: 0.413 AC: 28039 AN: 67954

Other (OTH) AF: 0.413 AC: 872 AN: 2112

Alfa AF: 0.408 Hom.: 19504

Bravo AF: 0.391

Asia WGS AF: 0.423 AC: 1473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.87
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1571011; hg19: chr10-90757787;