rs4147581

Variant names:

• chr11-67584114-C-G
• rs4147581
• NM_000852.4:c.2-20C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000852.4(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 NM_000852.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0170
• Publications: 53 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
GSTP1	NM_000852.4	c.2-20C>G		intron_variant	Intron 1 of 6	ENST00000398606.10	NP_000843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTP1	ENST00000398606.10	c.2-20C>G		intron_variant	Intron 1 of 6	1	NM_000852.4	ENSP00000381607.3

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

GnomAD2 exomes AF: 0.486 AC: 119389 AN: 245506 AF XY: 0.501

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 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

African (AFR) AF: 0.132 AC: 4410 AN: 33316

American (AMR) AF: 0.342 AC: 15217 AN: 44514

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 16809 AN: 25944

East Asian (EAS) AF: 0.669 AC: 26452 AN: 39532

South Asian (SAS) AF: 0.605 AC: 51928 AN: 85790

European-Finnish (FIN) AF: 0.501 AC: 26706 AN: 53290

Middle Eastern (MID) AF: 0.547 AC: 3054 AN: 5586

European-Non Finnish (NFE) AF: 0.482 AC: 527378 AN: 1094684

Other (OTH) AF: 0.494 AC: 29468 AN: 59680

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

African (AFR) AF: 0.145 AC: 6007 AN: 41478

American (AMR) AF: 0.401 AC: 6125 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2224 AN: 3470

East Asian (EAS) AF: 0.685 AC: 3462 AN: 5054

South Asian (SAS) AF: 0.625 AC: 3014 AN: 4826

European-Finnish (FIN) AF: 0.516 AC: 5428 AN: 10526

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33048 AN: 67866

Other (OTH) AF: 0.447 AC: 943 AN: 2108

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.1
DANN	Benign	0.49
PhyloP100		-0.017
PromoterAI		-0.013	Neutral
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

Other links and lift over

dbSNP: rs4147581; hg19: chr11-67351585;