chr2-85697261-C-G

Variant names:

• chr2-85697261-C-G
• rs1561285
• NM_006433.5:c.256-245C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006433.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNLY	NM_006433.5	MANE Select	c.256-245C>G		intron	N/A	NP_006424.2
	GNLY	NM_001302758.2		c.337-245C>G		intron	N/A	NP_001289687.1	B4E3H9
	GNLY	NM_012483.4		c.211-245C>G		intron	N/A	NP_036615.2	P22749-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNLY	ENST00000263863.9	TSL:1 MANE Select	c.256-245C>G		intron	N/A	ENSP00000263863.5	P22749-1
	GNLY	ENST00000409696.7	TSL:1	c.211-245C>G		intron	N/A	ENSP00000387116.3	P22749-2
	GNLY	ENST00000526018.1	TSL:5	c.154-245C>G		intron	N/A	ENSP00000434467.1	H0YDW8

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

African (AFR) AF: 0.485 AC: 5025 AN: 10354

American (AMR) AF: 0.433 AC: 6308 AN: 14580

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 5050 AN: 10700

East Asian (EAS) AF: 0.599 AC: 13508 AN: 22566

South Asian (SAS) AF: 0.353 AC: 12761 AN: 36108

European-Finnish (FIN) AF: 0.379 AC: 7804 AN: 20568

Middle Eastern (MID) AF: 0.426 AC: 647 AN: 1520

European-Non Finnish (NFE) AF: 0.379 AC: 76272 AN: 201104

Other (OTH) AF: 0.411 AC: 8152 AN: 19828

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

African (AFR) AF: 0.489 AC: 20274 AN: 41494

American (AMR) AF: 0.434 AC: 6635 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1613 AN: 3470

East Asian (EAS) AF: 0.610 AC: 3140 AN: 5150

South Asian (SAS) AF: 0.383 AC: 1852 AN: 4832

European-Finnish (FIN) AF: 0.387 AC: 4101 AN: 10588

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26289 AN: 67980

Other (OTH) AF: 0.451 AC: 952 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.7
DANN	Benign	0.68
PhyloP100		0.0040
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1561285; hg19: chr2-85924384;