Genetic Variant GZMB:c.*30A>G (chr14-24631041-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004131.6(GZMB):c.*30A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,577,874 control chromosomes in the GnomAD database, including 43,344 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 0.25 ( 4887 hom., cov: 32)

Exomes 𝑓: 0.23 ( 38457 hom. )

Consequence

GZMB
NM_004131.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.260

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:

ENSG00000258657 (HGNC:58166):

ENSG00000258657 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GZMB	NM_004131.6 link	c.*30A>G	3_prime_UTR_variant	Exon 5 of 5	ENST00000216341.9	NP_004122.2	P10144Q67BC3
GZMB	NM_001346011.2 link	c.*30A>G	3_prime_UTR_variant	Exon 5 of 5		NP_001332940.1	J3KQ52Q6XGZ4
GZMB	NR_144343.2 link	n.668A>G	non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GZMB	ENST00000216341 link	c.*30A>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_004131.6	ENSP00000216341.4		P10144

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

37862

AN:

152034

Hom.:

4872

Cov.:

show subpopulations

Gnomad AFR

AF:

0.313

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.246

Gnomad EAS

AF:

0.281

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.226

Gnomad OTH

AF:

0.261

GnomAD3 exomes

AF:

0.237

AC:

59028

AN:

249492

Hom.:

7432

AF XY:

0.244

AC XY:

32831

AN XY:

134784

show subpopulations

Gnomad AFR exome

AF:

0.320

Gnomad AMR exome

AF:

0.143

Gnomad ASJ exome

AF:

0.258

Gnomad EAS exome

AF:

0.280

Gnomad SAS exome

AF:

0.323

Gnomad FIN exome

AF:

0.186

Gnomad NFE exome

AF:

0.231

Gnomad OTH exome

AF:

0.231

GnomAD4 exome

AF:

0.228

AC:

324938

AN:

1425722

Hom.:

38457

Cov.:

AF XY:

0.232

AC XY:

164693

AN XY:

710950

show subpopulations

Gnomad4 AFR exome

AF:

0.320

Gnomad4 AMR exome

AF:

0.149

Gnomad4 ASJ exome

AF:

0.258

Gnomad4 EAS exome

AF:

0.233

Gnomad4 SAS exome

AF:

0.319

Gnomad4 FIN exome

AF:

0.192

Gnomad4 NFE exome

AF:

0.221

Gnomad4 OTH exome

AF:

0.245

GnomAD4 genome

AF:

0.249

AC:

37926

AN:

152152

Hom.:

4887

Cov.:

AF XY:

0.246

AC XY:

18334

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.314

Gnomad4 AMR

AF:

0.193

Gnomad4 ASJ

AF:

0.246

Gnomad4 EAS

AF:

0.281

Gnomad4 SAS

AF:

0.335

Gnomad4 FIN

AF:

0.182

Gnomad4 NFE

AF:

0.226

Gnomad4 OTH

AF:

0.264

Alfa

AF:

0.238

Hom.:

6184

Bravo

AF:

0.252

Asia WGS

AF:

0.332

AC:

1155

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.3

DANN

Benign

0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over