rs1695

Variant names:

• chr11-67585218-A-G
• rs1695
• NM_000852.4:c.313A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-67585218-A-G
• chr11-67585218-A-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.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. 14/20 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
• Conservation: PhyloP100: -1.46
• Publications: 1693 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=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 VariationId 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.

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.313A>G	p.Ile105Val	missense	Exon 5 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.313A>G	p.Ile105Val	missense	Exon 5 of 7	ENSP00000381607.3
	GSTP1	ENST00000495996.2	TSL:2	c.313A>G	p.Ile105Val	missense	Exon 5 of 7	ENSP00000484686.2
	GSTP1	ENST00000906565.1		c.313A>G	p.Ile105Val	missense	Exon 5 of 7	ENSP00000576624.1

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

GnomAD2 exomes AF: 0.339 AC: 84137 AN: 248500 AF XY: 0.329

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 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

African (AFR) AF: 0.455 AC: 15172 AN: 33322

American (AMR) AF: 0.505 AC: 22565 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 5706 AN: 26102

East Asian (EAS) AF: 0.161 AC: 6394 AN: 39654

South Asian (SAS) AF: 0.286 AC: 24591 AN: 86050

European-Finnish (FIN) AF: 0.275 AC: 14654 AN: 53278

Middle Eastern (MID) AF: 0.312 AC: 1793 AN: 5756

European-Non Finnish (NFE) AF: 0.346 AC: 382506 AN: 1105198

Other (OTH) AF: 0.333 AC: 20001 AN: 60140

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

African (AFR) AF: 0.443 AC: 18308 AN: 41334

American (AMR) AF: 0.420 AC: 6412 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 734 AN: 3464

East Asian (EAS) AF: 0.180 AC: 926 AN: 5138

South Asian (SAS) AF: 0.268 AC: 1293 AN: 4818

European-Finnish (FIN) AF: 0.263 AC: 2781 AN: 10586

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23035 AN: 67868

Other (OTH) AF: 0.347 AC: 733 AN: 2112

Alfa AF: 0.339 Hom.: 43261

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Abnormality of immune system physiology (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0087	N
LIST_S2	Benign	0.014	T
MetaRNN	Benign	0.000045	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.095	N
PhyloP100		-1.5
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.29	N
REVEL	Benign	0.013
Sift	Benign	1.0	T
Polyphen		0.0	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

Other links and lift over

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