Variant rs2273844 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000555300.1(ENSG00000258657):n.177+11082G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,562,184 control chromosomes in the GnomAD database, including 44,879 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 0.26 ( 5216 hom., cov: 32)

Exomes 𝑓: 0.23 ( 39663 hom. )

Consequence

ENST00000555300.1 intron, non_coding_transcript

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.129

Variant links:

Genes affected

(HGNC:):

links:

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:

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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=-0.75).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
LOC105370413	XR_007064087.1 linkuse as main transcript	n.248-88G>A	intron_variant, non_coding_transcript_variant
GZMB	NM_004131.6 linkuse as main transcript		upstream_gene_variant	ENST00000216341.9	NP_004122.2
GZMB	NM_001346011.2 linkuse as main transcript		upstream_gene_variant		NP_001332940.1
GZMB	NR_144343.2 linkuse as main transcript		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000555300.1 linkuse as main transcript	n.177+11082G>A		intron_variant, non_coding_transcript_variant		5
GZMB	ENST00000216341.9 linkuse as main transcript			upstream_gene_variant		1	NM_004131.6	ENSP00000216341	P2

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

38893

AN:

151942

Hom.:

5200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.336

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.228

Gnomad EAS

AF:

0.266

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.271

GnomAD3 exomes

AF:

0.242

AC:

42195

AN:

174628

Hom.:

5399

AF XY:

0.247

AC XY:

22640

AN XY:

91594

show subpopulations

Gnomad AFR exome

AF:

0.354

Gnomad AMR exome

AF:

0.152

Gnomad ASJ exome

AF:

0.250

Gnomad EAS exome

AF:

0.273

Gnomad SAS exome

AF:

0.318

Gnomad FIN exome

AF:

0.193

Gnomad NFE exome

AF:

0.236

Gnomad OTH exome

AF:

0.238

GnomAD4 exome

AF:

0.233

AC:

329047

AN:

1410124

Hom.:

39663

Cov.:

AF XY:

0.236

AC XY:

164042

AN XY:

696222

show subpopulations

Gnomad4 AFR exome

AF:

0.350

Gnomad4 AMR exome

AF:

0.160

Gnomad4 ASJ exome

AF:

0.246

Gnomad4 EAS exome

AF:

0.226

Gnomad4 SAS exome

AF:

0.315

Gnomad4 FIN exome

AF:

0.200

Gnomad4 NFE exome

AF:

0.226

Gnomad4 OTH exome

AF:

0.252

GnomAD4 genome

AF:

0.256

AC:

38955

AN:

152060

Hom.:

5216

Cov.:

AF XY:

0.253

AC XY:

18775

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.337

Gnomad4 AMR

AF:

0.196

Gnomad4 ASJ

AF:

0.228

Gnomad4 EAS

AF:

0.266

Gnomad4 SAS

AF:

0.329

Gnomad4 FIN

AF:

0.191

Gnomad4 NFE

AF:

0.227

Gnomad4 OTH

AF:

0.277

Alfa

AF:

0.240

Hom.:

6312

Bravo

AF:

0.260

Asia WGS

AF:

0.337

AC:

1174

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Uncertain

1.0

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