dbSNP rs1866138: GNLY:c.52+168A>G (chr2-85694638-A-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.52+168A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 1,066,024 control chromosomes in the GnomAD database, including 111,874 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 0.50 ( 19628 hom., cov: 34)

Exomes 𝑓: 0.45 ( 92246 hom. )

Consequence

GNLY
NM_006433.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.513

Publications

7 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNLY	NM_006433.5 link	c.52+168A>G		intron_variant	Intron 1 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.52+168A>G		intron_variant	Intron 1 of 4	1	NM_006433.5	ENSP00000263863.5		P22749-1

Frequencies

GnomAD3 genomes

AF:

0.500

AC:

75923

AN:

151936

Hom.:

19610

Cov.:

show subpopulations

Gnomad AFR

AF:

0.630

Gnomad AMI

AF:

0.603

Gnomad AMR

AF:

0.474

Gnomad ASJ

AF:

0.522

Gnomad EAS

AF:

0.583

Gnomad SAS

AF:

0.384

Gnomad FIN

AF:

0.412

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.439

Gnomad OTH

AF:

0.507

GnomAD4 exome

AF:

0.446

AC:

407201

AN:

913970

Hom.:

92246

Cov.:

AF XY:

0.444

AC XY:

203769

AN XY:

459102

show subpopulations

African (AFR)

AF:

0.639

AC:

13438

AN:

21026

American (AMR)

AF:

0.484

AC:

10468

AN:

21626

Ashkenazi Jewish (ASJ)

AF:

0.534

AC:

8992

AN:

16826

East Asian (EAS)

AF:

0.574

AC:

19343

AN:

33710

South Asian (SAS)

AF:

0.379

AC:

21716

AN:

57262

European-Finnish (FIN)

AF:

0.409

AC:

14388

AN:

35204

Middle Eastern (MID)

AF:

0.485

AC:

1413

AN:

2916

European-Non Finnish (NFE)

AF:

0.436

AC:

298050

AN:

683902

Other (OTH)

AF:

0.467

AC:

19393

AN:

41498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

11191

22382

33572

44763

55954

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7866

15732

23598

31464

39330

<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:

0.500

AC:

75987

AN:

152054

Hom.:

19628

Cov.:

AF XY:

0.496

AC XY:

36905

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.630

AC:

26145

AN:

41498

American (AMR)

AF:

0.473

AC:

7237

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.522

AC:

1811

AN:

3472

East Asian (EAS)

AF:

0.584

AC:

2999

AN:

5138

South Asian (SAS)

AF:

0.384

AC:

1853

AN:

4826

European-Finnish (FIN)

AF:

0.412

AC:

4355

AN:

10576

Middle Eastern (MID)

AF:

0.503

AC:

147

AN:

292

European-Non Finnish (NFE)

AF:

0.439

AC:

29819

AN:

67936

Other (OTH)

AF:

0.507

AC:

1072

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1992

3984

5976

7968

9960

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

664

1328

1992

2656

3320

<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:

0.455

Hom.:

11060

Bravo

AF:

0.515

Asia WGS

AF:

0.496

AC:

1721

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

6.5

(source)

DANN

Benign

0.75

PhyloP100

0.51

PromoterAI

0.017

Neutral

(source)

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