11-67585218-A-G

Position:

• chr11-67585218-A-G

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.313A>G​(p.Ile105Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,605,938 control chromosomes in the GnomAD database, including 96,157 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10253 hom., cov: 32)
  • Exomes 𝑓: 0.34 (85904 hom.)
• Consequence: GSTP1 NM_000852.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: -1.46

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 (MetaRNN=4.4708562E-5).
• BP6: Variant 11-67585218-A-G is Benign according to our data. Variant chr11-67585218-A-G is described in ClinVar as [Benign]. Clinvar id is 37340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTP1	NM_000852.4	c.313A>G	p.Ile105Val	missense_variant	5/7	ENST00000398606.10	NP_000843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTP1	ENST00000398606.10	c.313A>G	p.Ile105Val	missense_variant	5/7	1	NM_000852.4	ENSP00000381607	P1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54588 AN: 151674 Hom.: 10241 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.350

GnomAD3 exomes AF: 0.339 AC: 84137 AN: 248500 Hom.: 15539 AF XY: 0.329 AC XY: 44394 AN XY: 134908

Gnomad AFR exome AF: 0.448

Gnomad AMR exome AF: 0.519

Gnomad ASJ exome AF: 0.213

Gnomad EAS exome AF: 0.177

Gnomad SAS exome AF: 0.287

Gnomad FIN exome AF: 0.271

Gnomad NFE exome AF: 0.333

Gnomad OTH exome AF: 0.334

GnomAD4 exome AF: 0.339 AC: 493382 AN: 1454146 Hom.: 85904 Cov.: 31 AF XY: 0.336 AC XY: 242988 AN XY: 723844

Gnomad4 AFR exome AF: 0.455

Gnomad4 AMR exome AF: 0.505

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.161

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.275

Gnomad4 NFE exome AF: 0.346

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.360 AC: 54640 AN: 151792 Hom.: 10253 Cov.: 32 AF XY: 0.354 AC XY: 26226 AN XY: 74184

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.347

Alfa AF: 0.329 Hom.: 20651

Bravo AF: 0.380

TwinsUK AF: 0.350 AC: 1296

ALSPAC AF: 0.345 AC: 1328

ESP6500AA AF: 0.420 AC: 1749

ESP6500EA AF: 0.332 AC: 2786

ExAC AF: 0.332 AC: 40134

Asia WGS AF: 0.278 AC: 968 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3 Other:1

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 09, 2021	This variant is associated with the following publications: (PMID: 25799091, 26663067, 27984487, 25591549, 24582550, 24547706, 23977100, 24919441, 23979883, 24185126, 23552977, 27271084, 10376763, 23278642, 20674822, 17250723, 20091863, 9525277, 20840864, 19383894, 22960333, 23142420, 22525558, 22326267, 18988661, 22206016, 22251241, 9299520, 9281308, 20608166, 23826324, 19027952, 21128213, 20032816, 21993019, 23278115, 9092542, 20041472) -

Abnormality of immune system physiology Benign:1

Benign, no assertion criteria provided

reference population

iDNA Genomics

Sep 06, 2021

- -

Neoplasm of the large intestine Other:1

not provided, no classification provided

literature only

Database of Curated Mutations (DoCM)

Mar 10, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.0020
DANN	Benign	0.32
DEOGEN2	Benign	0.053	T;.;T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0087	N
LIST_S2	Benign	0.014	.;T;T
MetaRNN	Benign	0.000045	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.095	N;.;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.29	N;N;.
REVEL	Benign	0.013
Sift	Benign	1.0	T;T;.
Polyphen		0.0	B;.;B
Vest4		0.018
MPC		0.028
ClinPred		0.0015	T
GERP RS		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.4
Varity_R		0.18
gMVP		0.079

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: rs1695; hg19: chr11-67352689; COSMIC: COSV66992376; COSMIC: COSV66992376;