rs10873219

Positions:

• chr14-24632500-G-T

Variant summary

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

The NM_004131.6(GZMB):​c.204-41C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,612,180 control chromosomes in the GnomAD database, including 31,633 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 0.20 (2873 hom., cov: 31)
  • Exomes 𝑓: 0.20 (28760 hom.)
• Consequence: GZMB NM_004131.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.974

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]

ENSG00000258657 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GZMB	NM_004131.6	c.204-41C>A		intron_variant		ENST00000216341.9	NP_004122.2
GZMB	NM_001346011.2	c.168-41C>A		intron_variant			NP_001332940.1
GZMB	NR_144343.2	n.234-382C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GZMB	ENST00000216341.9	c.204-41C>A		intron_variant		1	NM_004131.6	ENSP00000216341.4

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29656 AN: 151768 Hom.: 2863 Cov.: 31

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.202

GnomAD3 exomes AF: 0.194 AC: 48529 AN: 250480 Hom.: 4867 AF XY: 0.199 AC XY: 26932 AN XY: 135352

Gnomad AFR exome AF: 0.213

Gnomad AMR exome AF: 0.129

Gnomad ASJ exome AF: 0.209

Gnomad EAS exome AF: 0.175

Gnomad SAS exome AF: 0.238

Gnomad FIN exome AF: 0.180

Gnomad NFE exome AF: 0.203

Gnomad OTH exome AF: 0.188

GnomAD4 exome AF: 0.196 AC: 286762 AN: 1460292 Hom.: 28760 Cov.: 33 AF XY: 0.198 AC XY: 144004 AN XY: 726486

Gnomad4 AFR exome AF: 0.213

Gnomad4 AMR exome AF: 0.133

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.147

Gnomad4 SAS exome AF: 0.239

Gnomad4 FIN exome AF: 0.183

Gnomad4 NFE exome AF: 0.197

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.195 AC: 29673 AN: 151888 Hom.: 2873 Cov.: 31 AF XY: 0.192 AC XY: 14268 AN XY: 74232

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.207

Alfa AF: 0.203 Hom.: 4577

Bravo AF: 0.194

Asia WGS AF: 0.225 AC: 784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.42

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: rs10873219; hg19: chr14-25101706; COSMIC: COSV53542960;