ENST00000557736.5:n.600T>C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

Genes affected

ENSG00000258657 (HGNC:58166):

LOC105370413 (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=-0.92).
• 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
LOC105370413	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	ENST00000555300.1	n.177+11330T>C		intron_variant	Intron 2 of 3	5
GZMB	ENST00000415355.7	c.-345A>G		upstream_gene_variant		2		ENSP00000387385.3
GZMB	ENST00000382540.5	c.-296A>G		upstream_gene_variant		5		ENSP00000371980.1

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

Gnomad4 AFR exome AF: 0.440

Gnomad4 AMR exome AF: 0.332

Gnomad4 ASJ exome AF: 0.606

Gnomad4 EAS exome AF: 0.457

Gnomad4 SAS exome AF: 0.615

Gnomad4 FIN exome AF: 0.554

Gnomad4 NFE exome AF: 0.606

Gnomad4 OTH exome AF: 0.568

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

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.604

Gnomad4 OTH AF: 0.515

Alfa AF: 0.588 Hom.: 57626

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

Splicing

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

Publications

LitVar

Other links and lift over

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