22-23958473-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001080843.4(GSTT2B):c.352-15C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 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 0.65 (27330 hom., cov: 36)
  • Exomes 𝑓: 0.65 (271116 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSTT2B NM_001080843.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.474

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS2: High Homozygotes in GnomAdExome at 12713 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTT2B	NM_001080843.4	c.352-15C>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000290765.9
GSTT2B	NM_001363804.1	c.352-15C>G		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTT2B	ENST00000290765.9	c.352-15C>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001080843.4	P1
GSTT2B	ENST00000404172.3	c.352-15C>G		splice_polypyrimidine_tract_variant, intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 98061 AN: 149876 Hom.: 27303 Cov.: 36 FAILED QC

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.647

GnomAD3 exomes AF: 0.451 AC: 41501 AN: 92024 Hom.: 12713 AF XY: 0.445 AC XY: 21006 AN XY: 47170

Gnomad AFR exome AF: 0.603

Gnomad AMR exome AF: 0.412

Gnomad ASJ exome AF: 0.403

Gnomad EAS exome AF: 0.374

Gnomad SAS exome AF: 0.579

Gnomad FIN exome AF: 0.549

Gnomad NFE exome AF: 0.399

Gnomad OTH exome AF: 0.488

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.653 AC: 937025 AN: 1434020 Hom.: 271116 Cov.: 77 AF XY: 0.655 AC XY: 467992 AN XY: 714234

Gnomad4 AFR exome AF: 0.671

Gnomad4 AMR exome AF: 0.631

Gnomad4 ASJ exome AF: 0.637

Gnomad4 EAS exome AF: 0.492

Gnomad4 SAS exome AF: 0.726

Gnomad4 FIN exome AF: 0.666

Gnomad4 NFE exome AF: 0.654

Gnomad4 OTH exome AF: 0.647

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.654 AC: 98145 AN: 149998 Hom.: 27330 Cov.: 36 AF XY: 0.656 AC XY: 48009 AN XY: 73240

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.643

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.736

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.654

Gnomad4 OTH AF: 0.645

Alfa AF: 0.575 Hom.: 1382

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	8.0
Dann	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs140194; hg19: chr22-24300660; COSMIC: COSV51960464; COSMIC: COSV51960464;