NM_145870.3:c.15+1071A>G

Variant names:

• chr14-77322254-A-G
• rs2111699
• NM_145870.3:c.15+1071A>G

Variant summary

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

The NM_145870.3(GSTZ1):​c.15+1071A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,074 control chromosomes in the GnomAD database, including 7,665 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 0.31 (7665 hom., cov: 32)
• Consequence: GSTZ1 NM_145870.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.479

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTZ1	NM_145870.3	c.15+1071A>G		intron_variant	Intron 1 of 8	ENST00000216465.10	NP_665877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTZ1	ENST00000216465.10	c.15+1071A>G		intron_variant	Intron 1 of 8	1	NM_145870.3	ENSP00000216465.5

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47873 AN: 151958 Hom.: 7657 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.315 AC: 47889 AN: 152074 Hom.: 7665 Cov.: 32 AF XY: 0.313 AC XY: 23271 AN XY: 74348

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.292

Alfa AF: 0.308 Hom.: 3464

Bravo AF: 0.306

Asia WGS AF: 0.287 AC: 996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	10
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: rs2111699; hg19: chr14-77788597;