ENST00000557736.5:n.600T>C

Variant names:

• chr14-24634456-T-C
• rs7144366
• ENST00000557736.5:n.600T>C

Variant summary

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

The ENST00000557736.5(ENSG00000258657):​n.600T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 444,166 control chromosomes in the GnomAD database, including 71,132 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 0.53 (21534 hom., cov: 32)
  • Exomes 𝑓: 0.58 (49598 hom.)
• Consequence: ENSG00000258657 ENST00000557736.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.531
• Publications: 17 publications found

Genes affected

ENSG00000258657 (HGNC:58166):

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GZMH-AS1	XR_007064087.1	n.408T>C		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000258657	ENST00000557736.5	n.600T>C		non_coding_transcript_exon_variant	Exon 3 of 3	4
ENSG00000258657	ENST00000770595.1	n.395T>C		non_coding_transcript_exon_variant	Exon 3 of 5
ENSG00000258657	ENST00000770596.1	n.397T>C		non_coding_transcript_exon_variant	Exon 3 of 4

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79760 AN: 151838 Hom.: 21526 Cov.: 32

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.514

GnomAD4 exome AF: 0.577 AC: 168464 AN: 292208 Hom.: 49598 Cov.: 4 AF XY: 0.583 AC XY: 90848 AN XY: 155732

African (AFR) AF: 0.440 AC: 3742 AN: 8496

American (AMR) AF: 0.332 AC: 4565 AN: 13754

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 5117 AN: 8448

East Asian (EAS) AF: 0.457 AC: 7538 AN: 16484

South Asian (SAS) AF: 0.615 AC: 25776 AN: 41894

European-Finnish (FIN) AF: 0.554 AC: 8172 AN: 14740

Middle Eastern (MID) AF: 0.585 AC: 739 AN: 1264

European-Non Finnish (NFE) AF: 0.606 AC: 103605 AN: 170904

Other (OTH) AF: 0.568 AC: 9210 AN: 16224

GnomAD4 genome AF: 0.525 AC: 79804 AN: 151958 Hom.: 21534 Cov.: 32 AF XY: 0.521 AC XY: 38668 AN XY: 74282

African (AFR) AF: 0.430 AC: 17828 AN: 41414

American (AMR) AF: 0.395 AC: 6030 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2083 AN: 3470

East Asian (EAS) AF: 0.451 AC: 2328 AN: 5162

South Asian (SAS) AF: 0.615 AC: 2964 AN: 4816

European-Finnish (FIN) AF: 0.539 AC: 5704 AN: 10574

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.604 AC: 41066 AN: 67944

Other (OTH) AF: 0.515 AC: 1084 AN: 2104

Alfa AF: 0.580 Hom.: 108395

Bravo AF: 0.504

Asia WGS AF: 0.490 AC: 1706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.3
DANN	Benign	0.42
PhyloP100		-0.53
PromoterAI		-0.012	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7144366; hg19: chr14-25103662; COSMIC: COSV53543675;