Variant 14-24632342-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_004131.6(GZMB):c.321C>T(p.Asn107=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,519,772 control chromosomes in the GnomAD database, including 45,760 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.26 ( 5238 hom., cov: 29)

Exomes 𝑓: 0.22 ( 40522 hom. )

Consequence

GZMB
NM_004131.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.15

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 14-24632342-G-A is Benign according to our data. Variant chr14-24632342-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 769857.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.15 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GZMB	NM_004131.6 linkuse as main transcript	c.321C>T	p.Asn107=	synonymous_variant	3/5	ENST00000216341.9
GZMB	NM_001346011.2 linkuse as main transcript	c.285C>T	p.Asn95=	synonymous_variant	3/5
GZMB	NR_144343.2 linkuse as main transcript	n.234-224C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GZMB	ENST00000216341.9 linkuse as main transcript	c.321C>T	p.Asn107=	synonymous_variant	3/5	1	NM_004131.6	P2
	ENST00000555300.1 linkuse as main transcript	n.177+9216G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.257

AC:

38416

AN:

149558

Hom.:

5222

Cov.:

show subpopulations

Gnomad AFR

AF:

0.344

Gnomad AMI

AF:

0.128

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.246

Gnomad EAS

AF:

0.262

Gnomad SAS

AF:

0.320

Gnomad FIN

AF:

0.185

Gnomad MID

AF:

0.312

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.265

GnomAD3 exomes

AF:

0.194

AC:

42014

AN:

216556

Hom.:

7096

AF XY:

0.199

AC XY:

23161

AN XY:

116360

show subpopulations

Gnomad AFR exome

AF:

0.311

Gnomad AMR exome

AF:

0.121

Gnomad ASJ exome

AF:

0.233

Gnomad EAS exome

AF:

0.231

Gnomad SAS exome

AF:

0.294

Gnomad FIN exome

AF:

0.133

Gnomad NFE exome

AF:

0.176

Gnomad OTH exome

AF:

0.200

GnomAD4 exome

AF:

0.217

AC:

296956

AN:

1370092

Hom.:

40522

Cov.:

AF XY:

0.220

AC XY:

149633

AN XY:

681390

show subpopulations

Gnomad4 AFR exome

AF:

0.352

Gnomad4 AMR exome

AF:

0.133

Gnomad4 ASJ exome

AF:

0.249

Gnomad4 EAS exome

AF:

0.214

Gnomad4 SAS exome

AF:

0.304

Gnomad4 FIN exome

AF:

0.174

Gnomad4 NFE exome

AF:

0.209

Gnomad4 OTH exome

AF:

0.238

GnomAD4 genome

AF:

0.257

AC:

38478

AN:

149680

Hom.:

5238

Cov.:

AF XY:

0.253

AC XY:

18490

AN XY:

73076

show subpopulations

Gnomad4 AFR

AF:

0.344

Gnomad4 AMR

AF:

0.195

Gnomad4 ASJ

AF:

0.246

Gnomad4 EAS

AF:

0.262

Gnomad4 SAS

AF:

0.321

Gnomad4 FIN

AF:

0.185

Gnomad4 NFE

AF:

0.227

Gnomad4 OTH

AF:

0.271

Alfa

AF:

0.249

Hom.:

907

Asia WGS

AF:

0.335

AC:

1165

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 25, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.59

DANN

Benign

0.68

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over