2-85694266-G-C

Variant names:

• chr2-85694266-G-C
• rs1866139
• ENST00000488945.5:n.48-1054G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000488945.5(GNLY):​n.48-1054G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 667,456 control chromosomes in the GnomAD database, including 78,239 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 0.51 (20239 hom., cov: 32)
  • Exomes 𝑓: 0.47 (58000 hom.)
• Consequence: GNLY ENST00000488945.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 11 publications found

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]

ENSG00000310473 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNLY	NM_006433.5	c.-153G>C		upstream_gene_variant		ENST00000263863.9	NP_006424.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNLY	ENST00000263863.9	c.-153G>C		upstream_gene_variant		1	NM_006433.5	ENSP00000263863.5

Frequencies

GnomAD3 genomes AF: 0.507 AC: 77057 AN: 151972 Hom.: 20221 Cov.: 32

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.515

GnomAD4 exome AF: 0.472 AC: 243013 AN: 515366 Hom.: 58000 Cov.: 6 AF XY: 0.471 AC XY: 126875 AN XY: 269122

African (AFR) AF: 0.653 AC: 8917 AN: 13660

American (AMR) AF: 0.504 AC: 11701 AN: 23204

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 7726 AN: 14284

East Asian (EAS) AF: 0.589 AC: 18014 AN: 30566

South Asian (SAS) AF: 0.464 AC: 21505 AN: 46372

European-Finnish (FIN) AF: 0.409 AC: 17751 AN: 43414

Middle Eastern (MID) AF: 0.512 AC: 1508 AN: 2948

European-Non Finnish (NFE) AF: 0.454 AC: 142282 AN: 313076

Other (OTH) AF: 0.489 AC: 13609 AN: 27842

GnomAD4 genome AF: 0.507 AC: 77120 AN: 152090 Hom.: 20239 Cov.: 32 AF XY: 0.504 AC XY: 37513 AN XY: 74362

African (AFR) AF: 0.639 AC: 26512 AN: 41486

American (AMR) AF: 0.479 AC: 7323 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1821 AN: 3470

East Asian (EAS) AF: 0.593 AC: 3063 AN: 5166

South Asian (SAS) AF: 0.468 AC: 2260 AN: 4828

European-Finnish (FIN) AF: 0.409 AC: 4321 AN: 10570

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.442 AC: 30032 AN: 67966

Other (OTH) AF: 0.514 AC: 1087 AN: 2114

Alfa AF: 0.476 Hom.: 2330

Bravo AF: 0.521

Asia WGS AF: 0.537 AC: 1864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.40
DANN	Benign	0.51
PhyloP100		-1.5
PromoterAI		-0.059	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1866139; hg19: chr2-85921389; COSMIC: COSV55704789;