Genetic Variant GNLY:n.48-1054G>A (chr2-85694266-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000488945.5(GNLY):n.48-1054G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000194 in 516,352 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000019 ( 0 hom. )

Consequence

GNLY
ENST00000488945.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.45

Publications

11 publications found

Variant links:

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]

GNLY links:

ENSG00000310473 (HGNC:):

ENSG00000310473 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNLY	NM_006433.5 link	c.-153G>A		upstream_gene_variant		ENST00000263863.9	NP_006424.2	P22749-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNLY	ENST00000263863.9 link	c.-153G>A		upstream_gene_variant		1	NM_006433.5	ENSP00000263863.5		P22749-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000194

AC:

AN:

516352

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

269630

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

13686

American (AMR)

AF:

0.00

AC:

AN:

23268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14308

East Asian (EAS)

AF:

0.00

AC:

AN:

30628

South Asian (SAS)

AF:

0.00

AC:

AN:

46446

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43480

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2950

European-Non Finnish (NFE)

AF:

0.00000319

AC:

AN:

313694

Other (OTH)

AF:

0.00

AC:

AN:

27892

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.47

(source)

DANN

Benign

0.88

PhyloP100

-1.5

PromoterAI

0.022

Neutral

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over