Genetic Variant ENSG00000258657:n.600T>A (chr14-24634456-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000557736.5(ENSG00000258657):n.600T>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ENSG00000258657
ENST00000557736.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.531

Publications

17 publications found

Variant links:

Genes affected

ENSG00000258657 (HGNC:58166):

ENSG00000258657 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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ENSG00000258657	ENST00000557736.5 link	n.600T>A	non_coding_transcript_exon_variant	Exon 3 of 3	4
ENSG00000258657	ENST00000770595.1 link	n.395T>A	non_coding_transcript_exon_variant	Exon 3 of 5
ENSG00000258657	ENST00000770596.1 link	n.397T>A	non_coding_transcript_exon_variant	Exon 3 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

293184

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

156260

African (AFR)

AF:

0.00

AC:

AN:

8540

American (AMR)

AF:

0.00

AC:

AN:

13812

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8486

East Asian (EAS)

AF:

0.00

AC:

AN:

16540

South Asian (SAS)

AF:

0.00

AC:

AN:

42016

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14788

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1266

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

171452

Other (OTH)

AF:

0.00

AC:

AN:

16284

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.8

(source)

DANN

Benign

0.44

PhyloP100

-0.53

PromoterAI

0.012

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over