rs10458360

Positions:

• chr1-172664835-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000367721.3(FASLG):​c.451+445G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 152,100 control chromosomes in the GnomAD database, including 27,265 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 0.56 (27265 hom., cov: 32)
• Consequence: FASLG ENST00000367721.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FASLG	NM_000639.3	c.451+445G>C		intron_variant		ENST00000367721.3	NP_000630.1
FASLG	NM_001302746.2	c.*21+445G>C		intron_variant			NP_001289675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FASLG	ENST00000367721.3	c.451+445G>C		intron_variant		1	NM_000639.3	ENSP00000356694	P1
FASLG	ENST00000340030.4	c.*21+445G>C		intron_variant		1		ENSP00000344739

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85251 AN: 151982 Hom.: 27216 Cov.: 32

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.561 AC: 85350 AN: 152100 Hom.: 27265 Cov.: 32 AF XY: 0.558 AC XY: 41457 AN XY: 74330

Gnomad4 AFR AF: 0.865

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.711

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.560

Alfa AF: 0.481 Hom.: 2949

Bravo AF: 0.581

Asia WGS AF: 0.569 AC: 1978 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.50
DANN	Benign	0.56

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: rs10458360; hg19: chr1-172633975;