rs1622002

Variant names:

• chr22-23958393-C-T
• rs1622002
• NM_001080843.4:c.417G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080843.4(GSTT2B):​c.417G>A​(p.Met139Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0316 in 1,428,374 control chromosomes in the GnomAD database, including 1,675 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.066 (334 hom., cov: 19)
  • Exomes 𝑓: 0.032 (1675 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSTT2B NM_001080843.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.578
• Publications: 16 publications found

Genes affected

GSTT2B (HGNC:33437): (glutathione S-transferase theta 2B) The protein encoded by this gene, glutathione S-transferase (GST) theta 2B (GSTT2B), 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 GSTT2B gene is a pseudogene in some populations. [provided by RefSeq, Sep 2015]

ENSG00000290199 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004102975).
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTT2B	NM_001080843.4	c.417G>A	p.Met139Ile	missense_variant	Exon 4 of 5	ENST00000290765.9	NP_001074312.1
GSTT2B	NM_001363804.1	c.417G>A	p.Met139Ile	missense_variant	Exon 4 of 5		NP_001350733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTT2B	ENST00000290765.9	c.417G>A	p.Met139Ile	missense_variant	Exon 4 of 5	1	NM_001080843.4	ENSP00000290765.4

Frequencies

GnomAD3 genomes AF: 0.0661 AC: 9882 AN: 149544 Hom.: 334 Cov.: 19

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0268

Gnomad AMR AF: 0.0595

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.0604

Gnomad FIN AF: 0.00514

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.0212

Gnomad OTH AF: 0.0563

GnomAD2 exomes AF: 0.0530 AC: 12869 AN: 242684 AF XY: 0.0486

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.0828

Gnomad ASJ exome AF: 0.0338

Gnomad EAS exome AF: 0.197

Gnomad FIN exome AF: 0.00543

Gnomad NFE exome AF: 0.0191

Gnomad OTH exome AF: 0.0426

GnomAD4 exome AF: 0.0316 AC: 45122 AN: 1428374 Hom.: 1675 Cov.: 29 AF XY: 0.0316 AC XY: 22497 AN XY: 711414

African (AFR) AF: 0.156 AC: 5034 AN: 32172

American (AMR) AF: 0.0781 AC: 3413 AN: 43716

Ashkenazi Jewish (ASJ) AF: 0.0350 AC: 902 AN: 25764

East Asian (EAS) AF: 0.192 AC: 7544 AN: 39204

South Asian (SAS) AF: 0.0528 AC: 4440 AN: 84020

European-Finnish (FIN) AF: 0.00601 AC: 318 AN: 52948

Middle Eastern (MID) AF: 0.0640 AC: 362 AN: 5652

European-Non Finnish (NFE) AF: 0.0186 AC: 20244 AN: 1085776

Other (OTH) AF: 0.0485 AC: 2865 AN: 59122

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0662 AC: 9906 AN: 149656 Hom.: 334 Cov.: 19 AF XY: 0.0661 AC XY: 4830 AN XY: 73024

African (AFR) AF: 0.150 AC: 6025 AN: 40198

American (AMR) AF: 0.0596 AC: 897 AN: 15056

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 117 AN: 3438

East Asian (EAS) AF: 0.187 AC: 929 AN: 4972

South Asian (SAS) AF: 0.0607 AC: 284 AN: 4682

European-Finnish (FIN) AF: 0.00514 AC: 54 AN: 10496

Middle Eastern (MID) AF: 0.0897 AC: 26 AN: 290

European-Non Finnish (NFE) AF: 0.0212 AC: 1433 AN: 67548

Other (OTH) AF: 0.0563 AC: 117 AN: 2080

Alfa AF: 0.0391 Hom.: 113

ESP6500AA AF: 0.140 AC: 615

ESP6500EA AF: 0.0193 AC: 166

ExAC AF: 0.0540 AC: 6552

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.1
DANN	Benign	0.82
DEOGEN2	Benign	0.0050	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.41	T;T
MetaRNN	Benign	0.0041	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.94	L;.
PhyloP100		-0.58
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.55	N;N
REVEL	Benign	0.048
Sift	Benign	0.18	T;T
Sift4G	Benign	0.069	T;T
Vest4		0.079
ClinPred		0.0021	T
GERP RS		-0.12
Varity_R		0.090
gMVP		0.42
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1622002; hg19: chr22-24300580; COSMIC: COSV99321064; COSMIC: COSV99321064;