Genetic Variant ENST00000313771.10:n.336G>C (chr10-88991623-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000313771.10(FAS):n.336G>C 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 0.299 in 153,676 control chromosomes in the GnomAD database, including 7,404 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 0.30 ( 7313 hom., cov: 33)

Exomes 𝑓: 0.36 ( 91 hom. )

Consequence

FAS
ENST00000313771.10 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.416

Publications

17 publications found

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:

ENSG00000286116 (HGNC:):

ENSG00000286116 links:

FAS-AS1 (HGNC:37128): (FAS antisense RNA 1)

FAS-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAS	NM_000043.6 link	c.30+717G>C		intron_variant	Intron 1 of 8	ENST00000652046.1	NP_000034.1	P25445-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAS	ENST00000652046.1 link	c.30+717G>C		intron_variant	Intron 1 of 8		NM_000043.6	ENSP00000498466.1		P25445-1

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

45430

AN:

152010

Hom.:

7305

Cov.:

show subpopulations

Gnomad AFR

AF:

0.237

Gnomad AMI

AF:

0.298

Gnomad AMR

AF:

0.313

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.0216

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.288

GnomAD4 exome

AF:

0.357

AC:

552

AN:

1548

Hom.:

Cov.:

AF XY:

0.343

AC XY:

293

AN XY:

854

show subpopulations

African (AFR)

AF:

0.333

AC:

AN:

American (AMR)

AF:

0.388

AC:

AN:

206

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.261

AC:

AN:

218

European-Finnish (FIN)

AF:

0.429

AC:

AN:

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.377

AC:

386

AN:

1024

Other (OTH)

AF:

0.300

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.299

AC:

45463

AN:

152128

Hom.:

7313

Cov.:

AF XY:

0.297

AC XY:

22082

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.236

AC:

9799

AN:

41496

American (AMR)

AF:

0.314

AC:

4803

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.278

AC:

964

AN:

3470

East Asian (EAS)

AF:

0.0215

AC:

111

AN:

5172

South Asian (SAS)

AF:

0.202

AC:

973

AN:

4822

European-Finnish (FIN)

AF:

0.342

AC:

3621

AN:

10582

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.356

AC:

24221

AN:

67978

Other (OTH)

AF:

0.291

AC:

615

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1571

3142

4714

6285

7856

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

448

896

1344

1792

2240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.332

Hom.:

1040

Bravo

AF:

0.298

Asia WGS

AF:

0.140

AC:

486

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.3

(source)

DANN

Benign

0.56

PhyloP100

0.42

PromoterAI

-0.026

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over