1-172661671-A-G

Position:

• chr1-172661671-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FASLG	NM_000639.3	c.394+1531A>G		intron_variant		ENST00000367721.3	NP_000630.1
FASLG	NM_001302746.2	c.348+2122A>G		intron_variant			NP_001289675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FASLG	ENST00000367721.3	c.394+1531A>G		intron_variant		1	NM_000639.3	ENSP00000356694.2
FASLG	ENST00000340030.4	c.348+2122A>G		intron_variant		1		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

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.100

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.292

Alfa AF: 0.268 Hom.: 5098

Bravo AF: 0.261

Asia WGS AF: 0.265 AC: 924 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.7
DANN	Benign	0.73

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

Other links and lift over

dbSNP: rs6700734; hg19: chr1-172630811;