dbSNP rs1561285: GNLY:c.256-245C>G (chr2-85697261-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00400

Publications

9 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: 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNLY	NM_006433.5 link	c.256-245C>G		intron_variant	Intron 3 of 4	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.256-245C>G		intron_variant	Intron 3 of 4	1	NM_006433.5	ENSP00000263863.5		P22749-1

Frequencies

GnomAD3 genomes

AF:

0.430

AC:

65292

AN:

151992

Hom.:

14229

Cov.:

show subpopulations

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.:

AF XY:

0.398

AC XY:

70205

AN XY:

176310

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

3600

7200

10800

14400

18000

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

514

1028

1542

2056

2570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.430

AC:

65337

AN:

152110

Hom.:

14243

Cov.:

AF XY:

0.429

AC XY:

31916

AN XY:

74366

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1967

3934

5902

7869

9836

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

606

1212

1818

2424

3030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.68

PhyloP100

0.0040

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over