dbSNP rs10873219: GZMB:c.204-41C>A (chr14-24632500-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004131.6(GZMB):c.204-41C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,612,180 control chromosomes in the GnomAD database, including 31,633 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 0.20 ( 2873 hom., cov: 31)

Exomes 𝑓: 0.20 ( 28760 hom. )

Consequence

GZMB
NM_004131.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.974

Publications

20 publications found

Variant links:

Genes affected

GZMB (HGNC:4709): (granzyme B) This gene encodes a member of the granzyme subfamily of proteins, part of the peptidase S1 family of serine proteases. The encoded preproprotein is secreted by natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) and proteolytically processed to generate the active protease, which induces target cell apoptosis. This protein also processes cytokines and degrades extracellular matrix proteins, and these roles are implicated in chronic inflammation and wound healing. Expression of this gene may be elevated in human patients with cardiac fibrosis. [provided by RefSeq, Sep 2016]

GZMB links:

GZMH-AS1 (HGNC:58166):

GZMH-AS1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_004131.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004131.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GZMB	NM_004131.6	MANE Select	c.204-41C>A	intron	N/A	NP_004122.2	P10144
GZMB	NM_001346011.2		c.168-41C>A	intron	N/A	NP_001332940.1	J3KQ52
GZMB	NR_144343.2		n.234-382C>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GZMB	ENST00000216341.9	TSL:1 MANE Select	c.204-41C>A	intron	N/A	ENSP00000216341.4	P10144
GZMB	ENST00000415355.7	TSL:2	c.168-41C>A	intron	N/A	ENSP00000387385.3	J3KQ52
GZMB	ENST00000859020.1		c.144-41C>A	intron	N/A	ENSP00000529079.1

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

29656

AN:

151768

Hom.:

2863

Cov.:

show subpopulations

Gnomad AFR

AF:

0.207

Gnomad AMI

AF:

0.128

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.179

Gnomad SAS

AF:

0.245

Gnomad FIN

AF:

0.175

Gnomad MID

AF:

0.213

Gnomad NFE

AF:

0.198

Gnomad OTH

AF:

0.202

GnomAD2 exomes

AF:

0.194

AC:

48529

AN:

250480

AF XY:

0.199

show subpopulations

Gnomad AFR exome

AF:

0.213

Gnomad AMR exome

AF:

0.129

Gnomad ASJ exome

AF:

0.209

Gnomad EAS exome

AF:

0.175

Gnomad FIN exome

AF:

0.180

Gnomad NFE exome

AF:

0.203

Gnomad OTH exome

AF:

0.188

GnomAD4 exome

AF:

0.196

AC:

286762

AN:

1460292

Hom.:

28760

Cov.:

AF XY:

0.198

AC XY:

144004

AN XY:

726486

show subpopulations

African (AFR)

AF:

0.213

AC:

7122

AN:

33430

American (AMR)

AF:

0.133

AC:

5958

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

5392

AN:

26068

East Asian (EAS)

AF:

0.147

AC:

5822

AN:

39682

South Asian (SAS)

AF:

0.239

AC:

20624

AN:

86146

European-Finnish (FIN)

AF:

0.183

AC:

9756

AN:

53384

Middle Eastern (MID)

AF:

0.241

AC:

1391

AN:

5762

European-Non Finnish (NFE)

AF:

0.197

AC:

218459

AN:

1110842

Other (OTH)

AF:

0.203

AC:

12238

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

Heterozygous variant carriers

12482

24964

37445

49927

62409

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7590

15180

22770

30360

37950

<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:

0.195

AC:

29673

AN:

151888

Hom.:

2873

Cov.:

AF XY:

0.192

AC XY:

14268

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.207

AC:

8559

AN:

41398

American (AMR)

AF:

0.158

AC:

2411

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

677

AN:

3470

East Asian (EAS)

AF:

0.179

AC:

919

AN:

5144

South Asian (SAS)

AF:

0.246

AC:

1178

AN:

4784

European-Finnish (FIN)

AF:

0.175

AC:

1851

AN:

10562

Middle Eastern (MID)

AF:

0.212

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.198

AC:

13462

AN:

67946

Other (OTH)

AF:

0.207

AC:

438

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1190

2380

3570

4760

5950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<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:

0.201

Hom.:

6415

Bravo

AF:

0.194

Asia WGS

AF:

0.225

AC:

784

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.6

(source)

DANN

Benign

0.42

PhyloP100

0.97

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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