rs1561285

chr2-85697261-C-Gchr2-85697261-C-T

Variant summary

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

The NM_006433.5(GNLY):c.256-245C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 489,438 control chromosomes in the GnomAD database, including 42,615 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 0.43 (14243 hom., cov: 33)
  • Exomes 𝑓: 0.40 (28372 hom.)
• Consequence: GNLY NM_006433.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNLY	NM_006433.5	c.256-245C>G		intron_variant		ENST00000263863.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNLY	ENST00000263863.9	c.256-245C>G		intron_variant		1	NM_006433.5	P2

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65292 AN: 151992 Hom.: 14229 Cov.: 33

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.453

GnomAD4 exome AF: 0.402 AC: 135527 AN: 337328 Hom.: 28372 Cov.: 2 AF XY: 0.398 AC XY: 70205 AN XY: 176310

Gnomad4 AFR exome AF: 0.485

Gnomad4 AMR exome AF: 0.433

Gnomad4 ASJ exome AF: 0.472

Gnomad4 EAS exome AF: 0.599

Gnomad4 SAS exome AF: 0.353

Gnomad4 FIN exome AF: 0.379

Gnomad4 NFE exome AF: 0.379

Gnomad4 OTH exome AF: 0.411

GnomAD4 genome AF: 0.430 AC: 65337 AN: 152110 Hom.: 14243 Cov.: 33 AF XY: 0.429 AC XY: 31916 AN XY: 74366

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.610

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.451

Alfa AF: 0.413 Hom.: 1605

Bravo AF: 0.440

Asia WGS AF: 0.485 AC: 1686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	2.7
Dann	Benign	0.68

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: rs1561285; hg19: chr2-85924384;