rs140188

Positions:

• chr22-23981861-C-G

Variant summary

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

The ENST00000634759.1(GSTT2):​c.201-767C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 134,044 control chromosomes in the GnomAD database, including 40,235 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 0.73 (40235 hom., cov: 24)
• Consequence: GSTT2 ENST00000634759.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.890

Genes affected

GSTT2 (HGNC:4642): (glutathione S-transferase theta 2 (gene/pseudogene)) The protein encoded by this gene, glutathione S-transferase (GST) theta 2 (GSTT2), is a member of a superfamily of proteins that catalyze the conjugation of reduced glutathione to a variety of electrophilic and hydrophobic compounds. Human GSTs can be divided into five main classes: alpha, mu, pi, theta, and zeta. The theta class includes GSTT1, GSTT2, and GSTT2B. GSTT2 and GSTT2B are nearly identical to each other, and share 55% amino acid identity with GSTT1. All three genes may play a role in human carcinogenesis. The GSTT2 gene is a pseudogene in some populations. [provided by RefSeq, Sep 2015]

GSTT3P (HGNC:55078): (glutathione S-transferase theta 3, pseudogene)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTT2	NR_126445.2	n.265-767C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTT2	ENST00000402588.6	c.201-767C>G		intron_variant		1		A2
GSTT2	ENST00000634759.1	c.201-767C>G		intron_variant		1		P5
GSTT3P	ENST00000437021.2	n.327-4284G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.732 AC: 98086 AN: 133942 Hom.: 40205 Cov.: 24

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.716

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

GnomAD4 genome AF: 0.732 AC: 98156 AN: 134044 Hom.: 40235 Cov.: 24 AF XY: 0.732 AC XY: 47949 AN XY: 65484

Gnomad4 AFR AF: 0.807

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.488

Gnomad4 SAS AF: 0.791

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.721

Gnomad4 OTH AF: 0.712

Alfa AF: 0.734 Hom.: 4976

Asia WGS AF: 0.663 AC: 2269 AN: 3420

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.26
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs140188; hg19: chr22-24324052;