chr1-172662917-A-G

Variant names:

• chr1-172662917-A-G
• rs929087
• NM_000639.3:c.395-1417A>G

Variant summary

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

The NM_000639.3(FASLG):​c.395-1417A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 151,862 control chromosomes in the GnomAD database, including 34,571 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 0.65 (34571 hom., cov: 30)
• Consequence: FASLG NM_000639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520
• Publications: 21 publications found

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 Gene-Disease associations (from GenCC):

• autoimmune lymphoproliferative syndrome type 1

  Inheritance: AD, AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• autoimmune lymphoproliferative syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FASLG	NM_000639.3	c.395-1417A>G		intron_variant	Intron 2 of 3	ENST00000367721.3	NP_000630.1
FASLG	NM_001302746.2	c.349-1417A>G		intron_variant	Intron 1 of 2		NP_001289675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FASLG	ENST00000367721.3	c.395-1417A>G		intron_variant	Intron 2 of 3	1	NM_000639.3	ENSP00000356694.2
FASLG	ENST00000340030.4	c.349-1417A>G		intron_variant	Intron 1 of 2	1		ENSP00000344739.3

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98653 AN: 151744 Hom.: 34507 Cov.: 30

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.658

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

GnomAD4 genome AF: 0.650 AC: 98764 AN: 151862 Hom.: 34571 Cov.: 30 AF XY: 0.646 AC XY: 47955 AN XY: 74206

African (AFR) AF: 0.911 AC: 37766 AN: 41442

American (AMR) AF: 0.578 AC: 8811 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 2358 AN: 3470

East Asian (EAS) AF: 0.471 AC: 2421 AN: 5142

South Asian (SAS) AF: 0.752 AC: 3611 AN: 4802

European-Finnish (FIN) AF: 0.433 AC: 4559 AN: 10534

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37143 AN: 67910

Other (OTH) AF: 0.663 AC: 1396 AN: 2106

Alfa AF: 0.588 Hom.: 57298

Bravo AF: 0.669

Asia WGS AF: 0.661 AC: 2299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.21
PhyloP100		0.052
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: rs929087; hg19: chr1-172632057;