rs4147581

Positions:

• chr11-67584114-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000398606.10(GSTP1):​c.2-20C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 1,594,156 control chromosomes in the GnomAD database, including 191,422 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (14431 hom., cov: 32)
  • Exomes 𝑓: 0.49 (176991 hom.)
• Consequence: GSTP1 ENST00000398606.10 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0170

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 11-67584114-C-G is Benign according to our data. Variant chr11-67584114-C-G is described in ClinVar as [Benign]. Clinvar id is 1268290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTP1	NM_000852.4	c.2-20C>G		intron_variant		ENST00000398606.10	NP_000843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTP1	ENST00000398606.10	c.2-20C>G		intron_variant		1	NM_000852.4	ENSP00000381607	P1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 60909 AN: 151702 Hom.: 14434 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.444

GnomAD3 exomes AF: 0.486 AC: 119389 AN: 245506 Hom.: 31291 AF XY: 0.501 AC XY: 66963 AN XY: 133618

Gnomad AFR exome AF: 0.138

Gnomad AMR exome AF: 0.337

Gnomad ASJ exome AF: 0.652

Gnomad EAS exome AF: 0.700

Gnomad SAS exome AF: 0.607

Gnomad FIN exome AF: 0.505

Gnomad NFE exome AF: 0.493

Gnomad OTH exome AF: 0.503

GnomAD4 exome AF: 0.486 AC: 701422 AN: 1442336 Hom.: 176991 Cov.: 32 AF XY: 0.493 AC XY: 354018 AN XY: 718674

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.342

Gnomad4 ASJ exome AF: 0.648

Gnomad4 EAS exome AF: 0.669

Gnomad4 SAS exome AF: 0.605

Gnomad4 FIN exome AF: 0.501

Gnomad4 NFE exome AF: 0.482

Gnomad4 OTH exome AF: 0.494

GnomAD4 genome AF: 0.401 AC: 60914 AN: 151820 Hom.: 14431 Cov.: 32 AF XY: 0.412 AC XY: 30582 AN XY: 74204

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.641

Gnomad4 EAS AF: 0.685

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.447

Alfa AF: 0.469 Hom.: 3570

Bravo AF: 0.380

Asia WGS AF: 0.601 AC: 2090 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.1
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4147581; hg19: chr11-67351585;