14-24631041-T-C

Variant names:

• chr14-24631041-T-C
• rs2236337
• NM_004131.6:c.*30A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004131.6(GZMB):​c.*30A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,577,874 control chromosomes in the GnomAD database, including 43,344 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 0.25 (4887 hom., cov: 32)
  • Exomes 𝑓: 0.23 (38457 hom.)
• Consequence: GZMB NM_004131.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.260
• Publications: 31 publications found

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]

GZMH-AS1 (HGNC:58166):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004131.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GZMB	NM_004131.6	MANE Select	c.*30A>G		3_prime_UTR	Exon 5 of 5	NP_004122.2	P10144
	GZMB	NM_001346011.2		c.*30A>G		3_prime_UTR	Exon 5 of 5	NP_001332940.1	J3KQ52
	GZMB	NR_144343.2		n.668A>G		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GZMB	ENST00000216341.9	TSL:1 MANE Select	c.*30A>G		3_prime_UTR	Exon 5 of 5	ENSP00000216341.4	P10144
	GZMB	ENST00000415355.7	TSL:2	c.*30A>G		3_prime_UTR	Exon 5 of 5	ENSP00000387385.3	J3KQ52
	GZMB	ENST00000859020.1		c.*30A>G		3_prime_UTR	Exon 5 of 5	ENSP00000529079.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37862 AN: 152034 Hom.: 4872 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.261

GnomAD2 exomes AF: 0.237 AC: 59028 AN: 249492 AF XY: 0.244

Gnomad AFR exome AF: 0.320

Gnomad AMR exome AF: 0.143

Gnomad ASJ exome AF: 0.258

Gnomad EAS exome AF: 0.280

Gnomad FIN exome AF: 0.186

Gnomad NFE exome AF: 0.231

Gnomad OTH exome AF: 0.231

GnomAD4 exome AF: 0.228 AC: 324938 AN: 1425722 Hom.: 38457 Cov.: 26 AF XY: 0.232 AC XY: 164693 AN XY: 710950

African (AFR) AF: 0.320 AC: 10399 AN: 32544

American (AMR) AF: 0.149 AC: 6621 AN: 44342

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 6648 AN: 25744

East Asian (EAS) AF: 0.233 AC: 9202 AN: 39424

South Asian (SAS) AF: 0.319 AC: 27138 AN: 85102

European-Finnish (FIN) AF: 0.192 AC: 10252 AN: 53348

Middle Eastern (MID) AF: 0.310 AC: 1758 AN: 5674

European-Non Finnish (NFE) AF: 0.221 AC: 238461 AN: 1080506

Other (OTH) AF: 0.245 AC: 14459 AN: 59038

GnomAD4 genome AF: 0.249 AC: 37926 AN: 152152 Hom.: 4887 Cov.: 32 AF XY: 0.246 AC XY: 18334 AN XY: 74390

African (AFR) AF: 0.314 AC: 13012 AN: 41482

American (AMR) AF: 0.193 AC: 2953 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 853 AN: 3470

East Asian (EAS) AF: 0.281 AC: 1454 AN: 5170

South Asian (SAS) AF: 0.335 AC: 1615 AN: 4828

European-Finnish (FIN) AF: 0.182 AC: 1934 AN: 10602

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15336 AN: 67982

Other (OTH) AF: 0.264 AC: 558 AN: 2110

Alfa AF: 0.240 Hom.: 7862

Bravo AF: 0.252

Asia WGS AF: 0.332 AC: 1155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
DANN	Benign	0.49
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2236337; hg19: chr14-25100247; COSMIC: COSV53540490; COSMIC: COSV53540490;