rs2287397

Positions:

• chr14-77330568-T-A

Variant summary

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

The NM_145870.3(GSTZ1):​c.524+209T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 152,224 control chromosomes in the GnomAD database, including 53 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 0.019 (53 hom., cov: 32)
• Consequence: GSTZ1 NM_145870.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTZ1	NM_145870.3	c.524+209T>A		intron_variant		ENST00000216465.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTZ1	ENST00000216465.10	c.524+209T>A		intron_variant		1	NM_145870.3

Frequencies

GnomAD3 genomes AF: 0.0192 AC: 2923 AN: 152106 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.00473

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0220

Gnomad ASJ AF: 0.0525

Gnomad EAS AF: 0.0206

Gnomad SAS AF: 0.0567

Gnomad FIN AF: 0.0163

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0231

Gnomad OTH AF: 0.0292

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0192 AC: 2919 AN: 152224 Hom.: 53 Cov.: 32 AF XY: 0.0198 AC XY: 1473 AN XY: 74420

Gnomad4 AFR AF: 0.00470

Gnomad4 AMR AF: 0.0219

Gnomad4 ASJ AF: 0.0525

Gnomad4 EAS AF: 0.0207

Gnomad4 SAS AF: 0.0563

Gnomad4 FIN AF: 0.0163

Gnomad4 NFE AF: 0.0231

Gnomad4 OTH AF: 0.0289

Alfa AF: 0.0209 Hom.: 6

Bravo AF: 0.0175

Asia WGS AF: 0.0290 AC: 102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.59
DANN	Benign	0.79

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: rs2287397; hg19: chr14-77796911;