rs749237778

Variant names:

• chr1-172659342-ACCACCGCCACCG-A
• NM_000639.3:c.147_158delGCCACCGCCACC

Your query was ambiguous. Multiple possible variants found:

• chr1-172659342-ACCACCGCCACCG-A
• chr1-172659342-ACCACCGCCACCG-ACCACCG
• chr1-172659342-ACCACCGCCACCG-ACCACCGCCACCGCCACCG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000639.3(FASLG):​c.147_158delGCCACCGCCACC​(p.Pro50_Pro53del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,864 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P49P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FASLG NM_000639.3 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.54

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FASLG	NM_000639.3	c.147_158delGCCACCGCCACC	p.Pro50_Pro53del	disruptive_inframe_deletion	Exon 1 of 4	ENST00000367721.3	NP_000630.1
FASLG	NM_001302746.2	c.147_158delGCCACCGCCACC	p.Pro50_Pro53del	disruptive_inframe_deletion	Exon 1 of 3		NP_001289675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FASLG	ENST00000367721.3	c.147_158delGCCACCGCCACC	p.Pro50_Pro53del	disruptive_inframe_deletion	Exon 1 of 4	1	NM_000639.3	ENSP00000356694.2
FASLG	ENST00000340030.4	c.147_158delGCCACCGCCACC	p.Pro50_Pro53del	disruptive_inframe_deletion	Exon 1 of 3	1		ENSP00000344739.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458864 Hom.: 0 AF XY: 0.00000138 AC XY: 1 AN XY: 725636

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-172628482;