rs5030772

chr1-172664210-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000639.3(FASLG):c.395-124A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 954,906 control chromosomes in the GnomAD database, including 8,417 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.099 (1080 hom., cov: 32)
  • Exomes 𝑓: 0.13 (7337 hom.)
• Consequence: FASLG NM_000639.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.181

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-172664210-A-G is Benign according to our data. Variant chr1-172664210-A-G is described in ClinVar as [Benign]. Clinvar id is 1273293.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FASLG	NM_000639.3	c.395-124A>G		intron_variant		ENST00000367721.3
FASLG	NM_001302746.2	c.349-124A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FASLG	ENST00000367721.3	c.395-124A>G		intron_variant		1	NM_000639.3	P1
FASLG	ENST00000340030.4	c.349-124A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0991 AC: 15081 AN: 152130 Hom.: 1079 Cov.: 32

Gnomad AFR AF: 0.0252

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.0983

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0940

Gnomad FIN AF: 0.0841

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.117

GnomAD4 exome AF: 0.127 AC: 101683 AN: 802658 Hom.: 7337 AF XY: 0.127 AC XY: 53106 AN XY: 417166

Gnomad4 AFR exome AF: 0.0234

Gnomad4 AMR exome AF: 0.0709

Gnomad4 ASJ exome AF: 0.183

Gnomad4 EAS exome AF: 0.000248

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.0926

Gnomad4 NFE exome AF: 0.144

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.0991 AC: 15081 AN: 152248 Hom.: 1080 Cov.: 32 AF XY: 0.0958 AC XY: 7132 AN XY: 74436

Gnomad4 AFR AF: 0.0251

Gnomad4 AMR AF: 0.0981

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0943

Gnomad4 FIN AF: 0.0841

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.115

Alfa AF: 0.117 Hom.: 141

Bravo AF: 0.0976

Asia WGS AF: 0.0420 AC: 146 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 08, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	5.9
Dann	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs5030772; hg19: chr1-172633350;