Variant 14-24631158-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_004131.6(GZMB):c.657T>C(p.Tyr219=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,611,976 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 9 hom. )

Consequence

GZMB
NM_004131.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.515

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 14-24631158-A-G is Benign according to our data. Variant chr14-24631158-A-G is described in ClinVar as [Benign]. Clinvar id is 774488.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.515 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GZMB	NM_004131.6 linkuse as main transcript	c.657T>C	p.Tyr219=	synonymous_variant	5/5	ENST00000216341.9
GZMB	NM_001346011.2 linkuse as main transcript	c.621T>C	p.Tyr207=	synonymous_variant	5/5
GZMB	NR_144343.2 linkuse as main transcript	n.551T>C		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GZMB	ENST00000216341.9 linkuse as main transcript	c.657T>C	p.Tyr219=	synonymous_variant	5/5	1	NM_004131.6	P2
	ENST00000555300.1 linkuse as main transcript	n.177+8032A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00193

AC:

294

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00285

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00188

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00166

AC:

418

AN:

251378

Hom.:

AF XY:

0.00195

AC XY:

265

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.00344

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00323

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00204

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00189

AC:

2757

AN:

1459696

Hom.:

Cov.:

AF XY:

0.00198

AC XY:

1436

AN XY:

726318

show subpopulations

Gnomad4 AFR exome

AF:

0.00338

Gnomad4 AMR exome

AF:

0.000693

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00310

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.00193

Gnomad4 OTH exome

AF:

0.00224

GnomAD4 genome

AF:

0.00197

AC:

300

AN:

152280

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

140

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00296

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00188

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00216

Hom.:

Bravo

AF:

0.00205

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00251

EpiControl

AF:

0.00267

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

Aug 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

1.5

DANN

Benign

0.60

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