rs749174

Positions:

• chr11-67585782-G-A

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.337-322G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 151,906 control chromosomes in the GnomAD database, including 6,808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.29 (6808 hom., cov: 30)
• Consequence: GSTP1 NM_000852.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.387

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=-0.64).
• BP6: Variant 11-67585782-G-A is Benign according to our data. Variant chr11-67585782-G-A is described in ClinVar as [Benign]. Clinvar id is 1253210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTP1	NM_000852.4	c.337-322G>A		intron_variant		ENST00000398606.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTP1	ENST00000398606.10	c.337-322G>A		intron_variant		1	NM_000852.4	P1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44379 AN: 151786 Hom.: 6800 Cov.: 30

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.306

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.292 AC: 44413 AN: 151906 Hom.: 6808 Cov.: 30 AF XY: 0.284 AC XY: 21078 AN XY: 74236

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.304

Alfa AF: 0.326 Hom.: 8072

Bravo AF: 0.289

Asia WGS AF: 0.231 AC: 804 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.64
CADD	Benign	7.7
DANN	Benign	0.91

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: rs749174; hg19: chr11-67353253;