Genetic Variant FASLG:c.-205C>G (chr1-172658997-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_000639.3(FASLG):c.-205C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 923,756 control chromosomes in the GnomAD database, including 838 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 568 hom., cov: 32)

Exomes 𝑓: 0.0053 ( 270 hom. )

Consequence

FASLG
NM_000639.3 upstream_gene

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.57

Variant links:

Genes affected

FASLG (HGNC:11936): (Fas ligand) This gene is a member of the tumor necrosis factor superfamily. The primary function of the encoded transmembrane protein is the induction of apoptosis triggered by binding to FAS. The FAS/FASLG signaling pathway is essential for immune system regulation, including activation-induced cell death (AICD) of T cells and cytotoxic T lymphocyte induced cell death. It has also been implicated in the progression of several cancers. Defects in this gene may be related to some cases of systemic lupus erythematosus (SLE). Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2014]

FASLG 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=-0.63).

BP6

Variant 1-172658997-C-G is Benign according to our data. Variant chr1-172658997-C-G is described in ClinVar as [Benign]. Clinvar id is 1272607.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FASLG	NM_000639.3 link	c.-205C>G		upstream_gene_variant		ENST00000367721.3	NP_000630.1	P48023-1Q53ZZ1
FASLG	NM_001302746.2 link	c.-205C>G		upstream_gene_variant			NP_001289675.1	P48023-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FASLG	ENST00000367721.3 link	c.-205C>G		upstream_gene_variant		1	NM_000639.3	ENSP00000356694.2		P48023-1
FASLG	ENST00000340030.4 link	c.-205C>G		upstream_gene_variant		1		ENSP00000344739.3		P48023-2

Frequencies

GnomAD3 genomes

AF:

0.0467

AC:

7109

AN:

152108

Hom.:

569

Cov.:

show subpopulations

Gnomad AFR

AF:

0.163

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0160

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.0278

GnomAD4 exome

AF:

0.00534

AC:

4118

AN:

771530

Hom.:

270

Cov.:

AF XY:

0.00456

AC XY:

1777

AN XY:

389576

show subpopulations

Gnomad4 AFR exome

AF:

0.167

Gnomad4 AMR exome

AF:

0.00858

Gnomad4 ASJ exome

AF:

0.00531

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000324

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000397

Gnomad4 OTH exome

AF:

0.0118

GnomAD4 genome

AF:

0.0467

AC:

7116

AN:

152226

Hom.:

568

Cov.:

AF XY:

0.0453

AC XY:

3370

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.163

Gnomad4 AMR

AF:

0.0160

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.0275

Alfa

AF:

0.00836

Hom.:

Bravo

AF:

0.0530

Asia WGS

AF:

0.00953

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 29, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.72

Splicing

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