1-172661671-A-G

Variant names:

• chr1-172661671-A-G
• rs6700734
• NM_000639.3:c.394+1531A>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.394+1531A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,060 control chromosomes in the GnomAD database, including 5,345 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 0.26 (5345 hom., cov: 32)
• Consequence: FASLG NM_000639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.400
• Publications: 11 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000639.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FASLG	NM_000639.3	MANE Select	c.394+1531A>G		intron	N/A	NP_000630.1
	FASLG	NM_001302746.2		c.348+2122A>G		intron	N/A	NP_001289675.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FASLG	ENST00000367721.3	TSL:1 MANE Select	c.394+1531A>G		intron	N/A	ENSP00000356694.2
	FASLG	ENST00000340030.4	TSL:1	c.348+2122A>G		intron	N/A	ENSP00000344739.3

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38805 AN: 151942 Hom.: 5327 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.256 AC: 38865 AN: 152060 Hom.: 5345 Cov.: 32 AF XY: 0.253 AC XY: 18775 AN XY: 74326

African (AFR) AF: 0.276 AC: 11436 AN: 41452

American (AMR) AF: 0.241 AC: 3678 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1422 AN: 3470

East Asian (EAS) AF: 0.100 AC: 520 AN: 5182

South Asian (SAS) AF: 0.389 AC: 1871 AN: 4804

European-Finnish (FIN) AF: 0.150 AC: 1587 AN: 10590

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17362 AN: 67978

Other (OTH) AF: 0.292 AC: 615 AN: 2106

Alfa AF: 0.260 Hom.: 13338

Bravo AF: 0.261

Asia WGS AF: 0.265 AC: 924 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.7
DANN	Benign	0.73
PhyloP100		0.40
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: rs6700734; hg19: chr1-172630811;