rs1871041

Positions:

• chr11-67584069-A-G
• chr11-67584069-A-T

Variant summary

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

The NM_000852.4(GSTP1):​c.2-65A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.909 in 1,373,348 control chromosomes in the GnomAD database, including 567,608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (59760 hom., cov: 32)
  • Exomes 𝑓: 0.91 (507848 hom.)
• Consequence: GSTP1 NM_000852.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.580

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=-0.88).
• BP6: Variant 11-67584069-A-G is Benign according to our data. Variant chr11-67584069-A-G is described in ClinVar as [Benign]. Clinvar id is 1274091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTP1	NM_000852.4	c.2-65A>G		intron_variant		ENST00000398606.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTP1	ENST00000398606.10	c.2-65A>G		intron_variant		1	NM_000852.4	P1
GSTP1	ENST00000398603.6	c.2-65A>G		intron_variant		3
GSTP1	ENST00000646888.1	c.2-65A>G		intron_variant, NMD_transcript_variant
GSTP1	ENST00000494593.1	n.24-65A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.887 AC: 134470 AN: 151622 Hom.: 59739 Cov.: 32

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.939

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.925

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.900

GnomAD4 exome AF: 0.911 AC: 1113182 AN: 1221610 Hom.: 507848 Cov.: 17 AF XY: 0.912 AC XY: 561892 AN XY: 616036

Gnomad4 AFR exome AF: 0.842

Gnomad4 AMR exome AF: 0.896

Gnomad4 ASJ exome AF: 0.914

Gnomad4 EAS exome AF: 0.833

Gnomad4 SAS exome AF: 0.922

Gnomad4 FIN exome AF: 0.843

Gnomad4 NFE exome AF: 0.920

Gnomad4 OTH exome AF: 0.910

GnomAD4 genome AF: 0.887 AC: 134546 AN: 151738 Hom.: 59760 Cov.: 32 AF XY: 0.885 AC XY: 65630 AN XY: 74122

Gnomad4 AFR AF: 0.841

Gnomad4 AMR AF: 0.891

Gnomad4 ASJ AF: 0.909

Gnomad4 EAS AF: 0.872

Gnomad4 SAS AF: 0.923

Gnomad4 FIN AF: 0.838

Gnomad4 NFE AF: 0.917

Gnomad4 OTH AF: 0.899

Alfa AF: 0.903 Hom.: 9120

Bravo AF: 0.889

Asia WGS AF: 0.898 AC: 3122 AN: 3474

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.0
DANN	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1871041; hg19: chr11-67351540;