rs2287395

Positions:

• chr14-77325176-A-G

Variant summary

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

The NM_145870.3(GSTZ1):​c.67+255A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 490,296 control chromosomes in the GnomAD database, including 23,534 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 0.30 (6992 hom., cov: 32)
  • Exomes 𝑓: 0.30 (16542 hom.)
• Consequence: GSTZ1 NM_145870.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758

Genes affected

GSTZ1 (HGNC:4643): (glutathione S-transferase zeta 1) This gene is a member of the glutathione S-transferase (GSTs) super-family which encodes multifunctional enzymes important in the detoxification of electrophilic molecules, including carcinogens, mutagens, and several therapeutic drugs, by conjugation with glutathione. This enzyme catalyzes the conversion of maleylacetoacetate to fumarylacetoacatate, which is one of the steps in the phenylalanine/tyrosine degradation pathway. Deficiency of a similar gene in mouse causes oxidative stress. Several transcript variants of this gene encode multiple protein isoforms. [provided by RefSeq, Jul 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTZ1	NM_145870.3	c.67+255A>G		intron_variant		ENST00000216465.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTZ1	ENST00000216465.10	c.67+255A>G		intron_variant		1	NM_145870.3

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45521 AN: 152014 Hom.: 6977 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.264

GnomAD4 exome AF: 0.304 AC: 102736 AN: 338164 Hom.: 16542 Cov.: 0 AF XY: 0.296 AC XY: 52697 AN XY: 178256

Gnomad4 AFR exome AF: 0.301

Gnomad4 AMR exome AF: 0.201

Gnomad4 ASJ exome AF: 0.285

Gnomad4 EAS exome AF: 0.475

Gnomad4 SAS exome AF: 0.180

Gnomad4 FIN exome AF: 0.382

Gnomad4 NFE exome AF: 0.310

Gnomad4 OTH exome AF: 0.304

GnomAD4 genome AF: 0.299 AC: 45557 AN: 152132 Hom.: 6992 Cov.: 32 AF XY: 0.298 AC XY: 22188 AN XY: 74366

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.271

Alfa AF: 0.290 Hom.: 8460

Bravo AF: 0.289

Asia WGS AF: 0.325 AC: 1126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.1
DANN	Benign	0.69

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: rs2287395; hg19: chr14-77791519;