rs2273844

chr14-24634208-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

Genes affected

(HGNC:):

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105370413	XR_007064087.1	n.248-88G>A		intron_variant, non_coding_transcript_variant
GZMB	NM_004131.6			upstream_gene_variant		ENST00000216341.9
GZMB	NM_001346011.2			upstream_gene_variant
GZMB	NR_144343.2			upstream_gene_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38893 AN: 151942 Hom.: 5200 Cov.: 32

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

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.: 32 AF XY: 0.236 AC XY: 164042 AN XY: 696222

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.: 32 AF XY: 0.253 AC XY: 18775 AN XY: 74348

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	13
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

Other links and lift over

dbSNP: rs2273844; hg19: chr14-25103414; COSMIC: COSV53540526; COSMIC: COSV53540526;