11-67586108-C-T

Variant names:

• chr11-67586108-C-T
• rs1138272
• NM_000852.4:c.341C>T

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.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. 12/20 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
• Publications: 421 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 (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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000852.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTP1	NM_000852.4	MANE Select	c.341C>T	p.Ala114Val	missense	Exon 6 of 7	NP_000843.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTP1	ENST00000398606.10	TSL:1 MANE Select	c.341C>T	p.Ala114Val	missense	Exon 6 of 7	ENSP00000381607.3
	GSTP1	ENST00000495996.2	TSL:2	c.341C>T	p.Ala114Val	missense	Exon 6 of 7	ENSP00000484686.2
	GSTP1	ENST00000914374.1		c.329C>T	p.Ala110Val	missense	Exon 6 of 7	ENSP00000584433.1

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

GnomAD2 exomes AF: 0.0593 AC: 14726 AN: 248494 AF XY: 0.0618

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 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

African (AFR) AF: 0.0121 AC: 404 AN: 33440

American (AMR) AF: 0.0251 AC: 1122 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.0394 AC: 1027 AN: 26080

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39676

South Asian (SAS) AF: 0.0693 AC: 5966 AN: 86114

European-Finnish (FIN) AF: 0.0822 AC: 4385 AN: 53374

Middle Eastern (MID) AF: 0.0726 AC: 418 AN: 5760

European-Non Finnish (NFE) AF: 0.0845 AC: 93574 AN: 1106904

Other (OTH) AF: 0.0700 AC: 4215 AN: 60212

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

African (AFR) AF: 0.0150 AC: 621 AN: 41414

American (AMR) AF: 0.0313 AC: 478 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0398 AC: 138 AN: 3468

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5172

South Asian (SAS) AF: 0.0624 AC: 300 AN: 4804

European-Finnish (FIN) AF: 0.0805 AC: 851 AN: 10574

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.0845 AC: 5737 AN: 67926

Other (OTH) AF: 0.0398 AC: 84 AN: 2110

Alfa AF: 0.0724 Hom.: 1587

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	-	Pulmonary disease, chronic obstructive, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.032
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
Vest4		0.13
MPC		0.036
ClinPred		0.0040	T
GERP RS		0.53
PromoterAI		-0.010	Neutral
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

Other links and lift over

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