11-67586373-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000852.4(GSTP1):c.445-16C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,599,400 control chromosomes in the GnomAD database, including 88,654 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7016 hom., cov: 32)
  • Exomes 𝑓: 0.33 (81638 hom.)
• Consequence: GSTP1 NM_000852.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0830

Genes affected

GSTP1 (HGNC:4638): (glutathione S-transferase pi 1) Glutathione S-transferases (GSTs) are a family of enzymes that play an important role in detoxification by catalyzing the conjugation of many hydrophobic and electrophilic compounds with reduced glutathione. Based on their biochemical, immunologic, and structural properties, the soluble GSTs are categorized into 4 main classes: alpha, mu, pi, and theta. This GST family member is a polymorphic gene encoding active, functionally different GSTP1 variant proteins that are thought to function in xenobiotic metabolism and play a role in susceptibility to cancer, and other diseases. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-67586373-C-T is Benign according to our data. Variant chr11-67586373-C-T is described in ClinVar as [Benign]. Clinvar id is 1288111.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTP1	NM_000852.4	c.445-16C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000398606.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTP1	ENST00000398606.10	c.445-16C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000852.4	P1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45160 AN: 152018 Hom.: 7007 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.306

GnomAD3 exomes AF: 0.281 AC: 67604 AN: 240862 Hom.: 10154 AF XY: 0.286 AC XY: 37329 AN XY: 130698

Gnomad AFR exome AF: 0.279

Gnomad AMR exome AF: 0.189

Gnomad ASJ exome AF: 0.211

Gnomad EAS exome AF: 0.151

Gnomad SAS exome AF: 0.259

Gnomad FIN exome AF: 0.281

Gnomad NFE exome AF: 0.341

Gnomad OTH exome AF: 0.309

GnomAD4 exome AF: 0.331 AC: 478795 AN: 1447264 Hom.: 81638 Cov.: 32 AF XY: 0.329 AC XY: 236412 AN XY: 718614

Gnomad4 AFR exome AF: 0.276

Gnomad4 AMR exome AF: 0.192

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.147

Gnomad4 SAS exome AF: 0.261

Gnomad4 FIN exome AF: 0.285

Gnomad4 NFE exome AF: 0.356

Gnomad4 OTH exome AF: 0.317

GnomAD4 genome AF: 0.297 AC: 45189 AN: 152136 Hom.: 7016 Cov.: 32 AF XY: 0.289 AC XY: 21492 AN XY: 74358

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.303

Alfa AF: 0.324 Hom.: 8456

Bravo AF: 0.294

Asia WGS AF: 0.229 AC: 799 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.8
Dann	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1871042; hg19: chr11-67353844; COSMIC: COSV66992473; COSMIC: COSV66992473;