Variant chr14-24632423-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004131.6(GZMB):c.240A>G(p.Lys80=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,547,436 control chromosomes in the GnomAD database, including 47,083 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5458 hom., cov: 30)

Exomes 𝑓: 0.22 ( 41625 hom. )

Consequence

GZMB
NM_004131.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.39

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BP6

Variant 14-24632423-T-C is Benign according to our data. Variant chr14-24632423-T-C is described in ClinVar as [Benign]. Clinvar id is 769859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.39 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GZMB	NM_004131.6 linkuse as main transcript	c.240A>G	p.Lys80=	synonymous_variant	3/5	ENST00000216341.9
GZMB	NM_001346011.2 linkuse as main transcript	c.204A>G	p.Lys68=	synonymous_variant	3/5
GZMB	NR_144343.2 linkuse as main transcript	n.234-305A>G		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.240A>G	p.Lys80=	synonymous_variant	3/5	1	NM_004131.6	P2
	ENST00000555300.1 linkuse as main transcript	n.177+9297T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39593

AN:

151342

Hom.:

5442

Cov.:

show subpopulations

Gnomad AFR

AF:

0.351

Gnomad AMI

AF:

0.132

Gnomad AMR

AF:

0.199

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.268

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.188

Gnomad MID

AF:

0.309

Gnomad NFE

AF:

0.229

Gnomad OTH

AF:

0.272

GnomAD3 exomes

AF:

0.181

AC:

37916

AN:

209180

Hom.:

7113

AF XY:

0.183

AC XY:

20384

AN XY:

111522

show subpopulations

Gnomad AFR exome

AF:

0.325

Gnomad AMR exome

AF:

0.101

Gnomad ASJ exome

AF:

0.172

Gnomad EAS exome

AF:

0.231

Gnomad SAS exome

AF:

0.244

Gnomad FIN exome

AF:

0.147

Gnomad NFE exome

AF:

0.171

Gnomad OTH exome

AF:

0.177

GnomAD4 exome

AF:

0.223

AC:

310642

AN:

1395976

Hom.:

41625

Cov.:

AF XY:

0.224

AC XY:

154845

AN XY:

691252

show subpopulations

Gnomad4 AFR exome

AF:

0.353

Gnomad4 AMR exome

AF:

0.118

Gnomad4 ASJ exome

AF:

0.237

Gnomad4 EAS exome

AF:

0.218

Gnomad4 SAS exome

AF:

0.297

Gnomad4 FIN exome

AF:

0.186

Gnomad4 NFE exome

AF:

0.217

Gnomad4 OTH exome

AF:

0.243

GnomAD4 genome

AF:

0.262

AC:

39653

AN:

151460

Hom.:

5458

Cov.:

AF XY:

0.258

AC XY:

19096

AN XY:

73986

show subpopulations

Gnomad4 AFR

AF:

0.351

Gnomad4 AMR

AF:

0.199

Gnomad4 ASJ

AF:

0.249

Gnomad4 EAS

AF:

0.268

Gnomad4 SAS

AF:

0.328

Gnomad4 FIN

AF:

0.188

Gnomad4 NFE

AF:

0.229

Gnomad4 OTH

AF:

0.278

Alfa

AF:

0.239

Hom.:

1046

Bravo

AF:

0.267

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

-1.0

CADD

Benign

2.1

DANN

Benign

0.43

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