Variant rs2296601 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000043.6(FAS):c.334+46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,611,144 control chromosomes in the GnomAD database, including 17,569 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2617 hom., cov: 32)

Exomes 𝑓: 0.13 ( 14952 hom. )

Consequence

FAS
NM_000043.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.346

Variant links:

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 links:

FAS (HGNC:):

FAS links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 10-89007883-C-T is Benign according to our data. Variant chr10-89007883-C-T is described in ClinVar as [Benign]. Clinvar id is 1235502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAS	NM_000043.6 linkuse as main transcript	c.334+46C>T		intron_variant		ENST00000652046.1	NP_000034.1	P25445-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAS	ENST00000652046.1 linkuse as main transcript	c.334+46C>T		intron_variant			NM_000043.6	ENSP00000498466.1		P25445-1

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25448

AN:

151918

Hom.:

2603

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.194

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.442

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.164

GnomAD3 exomes

AF:

0.165

AC:

41134

AN:

248930

Hom.:

4440

AF XY:

0.161

AC XY:

21715

AN XY:

134844

show subpopulations

Gnomad AFR exome

AF:

0.226

Gnomad AMR exome

AF:

0.191

Gnomad ASJ exome

AF:

0.0988

Gnomad EAS exome

AF:

0.450

Gnomad SAS exome

AF:

0.182

Gnomad FIN exome

AF:

0.170

Gnomad NFE exome

AF:

0.104

Gnomad OTH exome

AF:

0.148

GnomAD4 exome

AF:

0.126

AC:

184478

AN:

1459108

Hom.:

14952

Cov.:

AF XY:

0.127

AC XY:

92369

AN XY:

725930

show subpopulations

Gnomad4 AFR exome

AF:

0.225

Gnomad4 AMR exome

AF:

0.191

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.448

Gnomad4 SAS exome

AF:

0.179

Gnomad4 FIN exome

AF:

0.160

Gnomad4 NFE exome

AF:

0.103

Gnomad4 OTH exome

AF:

0.147

GnomAD4 genome

AF:

0.168

AC:

25498

AN:

152036

Hom.:

2617

Cov.:

AF XY:

0.172

AC XY:

12802

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.231

Gnomad4 AMR

AF:

0.194

Gnomad4 ASJ

AF:

0.105

Gnomad4 EAS

AF:

0.442

Gnomad4 SAS

AF:

0.200

Gnomad4 FIN

AF:

0.169

Gnomad4 NFE

AF:

0.105

Gnomad4 OTH

AF:

0.165

Alfa

AF:

0.128

Hom.:

264

Bravo

AF:

0.168

Asia WGS

AF:

0.346

AC:

1204

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 20% of patients studied by a panel of primary immunodeficiencies. Number of patients: 19. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.5

DANN

Benign

0.63

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over