rs1866138

Positions:

• chr2-85694638-A-G
• chr2-85694638-A-T

Variant summary

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

The NM_006433.5(GNLY):​c.52+168A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 1,066,024 control chromosomes in the GnomAD database, including 111,874 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 0.50 (19628 hom., cov: 34)
  • Exomes 𝑓: 0.45 (92246 hom.)
• Consequence: GNLY NM_006433.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.513

Genes affected

GNLY (HGNC:4414): (granulysin) The product of this gene is a member of the saposin-like protein (SAPLIP) family and is located in the cytotoxic granules of T cells, which are released upon antigen stimulation. This protein is present in cytotoxic granules of cytotoxic T lymphocytes and natural killer cells, and it has antimicrobial activity against M. tuberculosis and other organisms. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNLY	NM_006433.5	c.52+168A>G		intron_variant		ENST00000263863.9	NP_006424.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNLY	ENST00000263863.9	c.52+168A>G		intron_variant		1	NM_006433.5	ENSP00000263863	P2

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75923 AN: 151936 Hom.: 19610 Cov.: 34

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.507

GnomAD4 exome AF: 0.446 AC: 407201 AN: 913970 Hom.: 92246 Cov.: 12 AF XY: 0.444 AC XY: 203769 AN XY: 459102

Gnomad4 AFR exome AF: 0.639

Gnomad4 AMR exome AF: 0.484

Gnomad4 ASJ exome AF: 0.534

Gnomad4 EAS exome AF: 0.574

Gnomad4 SAS exome AF: 0.379

Gnomad4 FIN exome AF: 0.409

Gnomad4 NFE exome AF: 0.436

Gnomad4 OTH exome AF: 0.467

GnomAD4 genome AF: 0.500 AC: 75987 AN: 152054 Hom.: 19628 Cov.: 34 AF XY: 0.496 AC XY: 36905 AN XY: 74332

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.507

Alfa AF: 0.452 Hom.: 8990

Bravo AF: 0.515

Asia WGS AF: 0.496 AC: 1721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.5
DANN	Benign	0.75

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: rs1866138; hg19: chr2-85921761;