Genetic Variant GNLY:n.48-1054G>C (chr2-85694266-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.45

Publications

11 publications found

Variant links:

COSMIC-nc: COSV55704789

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=-1.0).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000488945.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GNLY	NM_006433.5	MANE Select	c.-153G>C	upstream_gene	N/A	NP_006424.2
GNLY	NM_001302758.2		c.-153G>C	upstream_gene	N/A	NP_001289687.1	B4E3H9
GNLY	NM_012483.4		c.-442G>C	upstream_gene	N/A	NP_036615.2	P22749-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
GNLY	ENST00000488945.5	TSL:1	n.48-1054G>C	intron	N/A
ENSG00000310473	ENST00000850261.1		n.932+3204C>G	intron	N/A
ENSG00000310473	ENST00000850262.1		n.567+3204C>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.507

AC:

77057

AN:

151972

Hom.:

20221

Cov.:

show subpopulations

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.:

AF XY:

0.471

AC XY:

126875

AN XY:

269122

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

6047

12095

18142

24190

30237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1544

3088

4632

6176

7720

<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:

0.507

AC:

77120

AN:

152090

Hom.:

20239

Cov.:

AF XY:

0.504

AC XY:

37513

AN XY:

74362

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1921

3842

5763

7684

9605

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

676

1352

2028

2704

3380

<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:

0.476

Hom.:

2330

Bravo

AF:

0.521

Asia WGS

AF:

0.537

AC:

1864

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.40

(source)

DANN

Benign

0.51

PhyloP100

-1.5

PromoterAI

-0.059

Neutral

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over