11-67586108-C-T

Position:

• chr11-67586108-C-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.341C>T​(p.Ala114Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0743 in 1,608,182 control chromosomes in the GnomAD database, including 5,074 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.055 (310 hom., cov: 31)
  • Exomes 𝑓: 0.076 (4764 hom.)
• Consequence: GSTP1 NM_000852.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: 0.0320

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=0.0015839636).
• BP6: Variant 11-67586108-C-T is Benign according to our data. Variant chr11-67586108-C-T is described in ClinVar as [Benign]. Clinvar id is 1264275.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTP1	NM_000852.4	c.341C>T	p.Ala114Val	missense_variant	6/7	ENST00000398606.10	NP_000843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTP1	ENST00000398606.10	c.341C>T	p.Ala114Val	missense_variant	6/7	1	NM_000852.4	ENSP00000381607	P1

Frequencies

GnomAD3 genomes AF: 0.0548 AC: 8315 AN: 151818 Hom.: 311 Cov.: 31

Gnomad AFR AF: 0.0150

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.0314

Gnomad ASJ AF: 0.0398

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0624

Gnomad FIN AF: 0.0805

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0845

Gnomad OTH AF: 0.0402

GnomAD3 exomes AF: 0.0593 AC: 14726 AN: 248494 Hom.: 565 AF XY: 0.0618 AC XY: 8333 AN XY: 134870

Gnomad AFR exome AF: 0.0133

Gnomad AMR exome AF: 0.0246

Gnomad ASJ exome AF: 0.0366

Gnomad EAS exome AF: 0.000167

Gnomad SAS exome AF: 0.0680

Gnomad FIN exome AF: 0.0850

Gnomad NFE exome AF: 0.0805

Gnomad OTH exome AF: 0.0564

GnomAD4 exome AF: 0.0763 AC: 111118 AN: 1456246 Hom.: 4764 Cov.: 30 AF XY: 0.0764 AC XY: 55344 AN XY: 724640

Gnomad4 AFR exome AF: 0.0121

Gnomad4 AMR exome AF: 0.0251

Gnomad4 ASJ exome AF: 0.0394

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.0693

Gnomad4 FIN exome AF: 0.0822

Gnomad4 NFE exome AF: 0.0845

Gnomad4 OTH exome AF: 0.0700

GnomAD4 genome AF: 0.0547 AC: 8310 AN: 151936 Hom.: 310 Cov.: 31 AF XY: 0.0538 AC XY: 3995 AN XY: 74254

Gnomad4 AFR AF: 0.0150

Gnomad4 AMR AF: 0.0313

Gnomad4 ASJ AF: 0.0398

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0624

Gnomad4 FIN AF: 0.0805

Gnomad4 NFE AF: 0.0845

Gnomad4 OTH AF: 0.0398

Alfa AF: 0.0742 Hom.: 604

Bravo AF: 0.0485

TwinsUK AF: 0.0790 AC: 293

ALSPAC AF: 0.0799 AC: 308

ESP6500AA AF: 0.0155 AC: 64

ESP6500EA AF: 0.0822 AC: 690

ExAC AF: 0.0595 AC: 7205

Asia WGS AF: 0.0250 AC: 86 AN: 3478

EpiCase AF: 0.0777

EpiControl AF: 0.0785

ClinVar

Significance: Benign

Submissions summary: Benign:2 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: 10780269, 23142420, 23437223, 9299520, 9092542) -

Pulmonary disease, chronic obstructive, susceptibility to Other:1

association, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Jul 05, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T;T;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.45	.;T;T
MetaRNN	Benign	0.0016	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	M;M;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.9	N;.;.
REVEL	Benign	0.086
Sift	Benign	0.25	T;.;.
Sift4G	Uncertain	0.028	.;.;D
Polyphen		0.55	P;P;.
Vest4		0.13
MPC		0.036
ClinPred		0.0040	T
GERP RS		0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.10

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: rs1138272; hg19: chr11-67353579; COSMIC: COSV66992270; COSMIC: COSV66992270;