Variant rs2296600 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.506-71C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 1,605,568 control chromosomes in the GnomAD database, including 130,037 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 11402 hom., cov: 32)

Exomes 𝑓: 0.40 ( 118635 hom. )

Consequence

FAS
NM_000043.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.557

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:

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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=-0.89).

BP6

Variant 10-89010682-C-G is Benign according to our data. Variant chr10-89010682-C-G is described in ClinVar as [Benign]. Clinvar id is 1291170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.487 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.506-71C>G		intron_variant		ENST00000652046.1	NP_000034.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAS	ENST00000652046.1 linkuse as main transcript	c.506-71C>G		intron_variant			NM_000043.6	ENSP00000498466	A2	P25445-1

Frequencies

GnomAD3 genomes

AF:

0.385

AC:

58543

AN:

151898

Hom.:

11403

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.422

Gnomad AMR

AF:

0.377

Gnomad ASJ

AF:

0.482

Gnomad EAS

AF:

0.503

Gnomad SAS

AF:

0.455

Gnomad FIN

AF:

0.409

Gnomad MID

AF:

0.436

Gnomad NFE

AF:

0.395

Gnomad OTH

AF:

0.404

GnomAD4 exome

AF:

0.402

AC:

583941

AN:

1453550

Hom.:

118635

Cov.:

AF XY:

0.404

AC XY:

292301

AN XY:

723764

show subpopulations

Gnomad4 AFR exome

AF:

0.340

Gnomad4 AMR exome

AF:

0.352

Gnomad4 ASJ exome

AF:

0.477

Gnomad4 EAS exome

AF:

0.484

Gnomad4 SAS exome

AF:

0.458

Gnomad4 FIN exome

AF:

0.414

Gnomad4 NFE exome

AF:

0.395

Gnomad4 OTH exome

AF:

0.412

GnomAD4 genome

AF:

0.385

AC:

58550

AN:

152018

Hom.:

11402

Cov.:

AF XY:

0.389

AC XY:

28941

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.333

Gnomad4 AMR

AF:

0.376

Gnomad4 ASJ

AF:

0.482

Gnomad4 EAS

AF:

0.503

Gnomad4 SAS

AF:

0.457

Gnomad4 FIN

AF:

0.409

Gnomad4 NFE

AF:

0.395

Gnomad4 OTH

AF:

0.401

Alfa

AF:

0.268

Hom.:

669

Bravo

AF:

0.382

Asia WGS

AF:

0.422

AC:

1464

AN:

3472

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 68% of patients studied by a panel of primary immunodeficiencies. Number of patients: 65. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.49

DANN

Benign

0.62

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