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GeneBe

14-24632423-T-C

Variant summary

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

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

2

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-1.01).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.39 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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 UniProt
GZMBNM_004131.6 linkuse as main transcriptc.240A>G p.Lys80= synonymous_variant 3/5 ENST00000216341.9
GZMBNM_001346011.2 linkuse as main transcriptc.204A>G p.Lys68= synonymous_variant 3/5
GZMBNR_144343.2 linkuse as main transcriptn.234-305A>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GZMBENST00000216341.9 linkuse as main transcriptc.240A>G p.Lys80= synonymous_variant 3/51 NM_004131.6 P2
ENST00000555300.1 linkuse as main transcriptn.177+9297T>C intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.262
AC:
39593
AN:
151342
Hom.:
5442
Cov.:
30
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.:
34
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.262
AC:
39653
AN:
151460
Hom.:
5458
Cov.:
30
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 submitterclinical testingInvitaeJul 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.

Other links and lift over

dbSNP: rs10909625; hg19: chr14-25101629; COSMIC: COSV53540581; API