Genetic Variant GSTP1:c.445-16C>T (chr11-67586373-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000852.4(GSTP1):c.445-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,599,400 control chromosomes in the GnomAD database, including 88,654 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7016 hom., cov: 32)

Exomes 𝑓: 0.33 ( 81638 hom. )

Consequence

GSTP1
NM_000852.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0830

Publications

48 publications found

Variant links:

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]

GSTP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 11-67586373-C-T is Benign according to our data. Variant chr11-67586373-C-T is described in ClinVar as Benign. ClinVar VariationId is 1288111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTP1	NM_000852.4 link	c.445-16C>T		intron_variant	Intron 6 of 6	ENST00000398606.10	NP_000843.1	P09211V9HWE9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTP1	ENST00000398606.10 link	c.445-16C>T		intron_variant	Intron 6 of 6	1	NM_000852.4	ENSP00000381607.3		P09211

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45160

AN:

152018

Hom.:

7007

Cov.:

show subpopulations

Gnomad AFR

AF:

0.276

Gnomad AMI

AF:

0.381

Gnomad AMR

AF:

0.228

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.153

Gnomad SAS

AF:

0.242

Gnomad FIN

AF:

0.274

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.306

GnomAD2 exomes

AF:

0.281

AC:

67604

AN:

240862

AF XY:

0.286

show subpopulations

Gnomad AFR exome

AF:

0.279

Gnomad AMR exome

AF:

0.189

Gnomad ASJ exome

AF:

0.211

Gnomad EAS exome

AF:

0.151

Gnomad FIN exome

AF:

0.281

Gnomad NFE exome

AF:

0.341

Gnomad OTH exome

AF:

0.309

GnomAD4 exome

AF:

0.331

AC:

478795

AN:

1447264

Hom.:

81638

Cov.:

AF XY:

0.329

AC XY:

236412

AN XY:

718614

show subpopulations

African (AFR)

AF:

0.276

AC:

9150

AN:

33138

American (AMR)

AF:

0.192

AC:

8360

AN:

43476

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

5504

AN:

25378

East Asian (EAS)

AF:

0.147

AC:

5796

AN:

39512

South Asian (SAS)

AF:

0.261

AC:

22220

AN:

85046

European-Finnish (FIN)

AF:

0.285

AC:

15094

AN:

53026

Middle Eastern (MID)

AF:

0.311

AC:

1770

AN:

5696

European-Non Finnish (NFE)

AF:

0.356

AC:

391979

AN:

1102274

Other (OTH)

AF:

0.317

AC:

18922

AN:

59718

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

14763

29526

44288

59051

73814

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12364

24728

37092

49456

61820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.297

AC:

45189

AN:

152136

Hom.:

7016

Cov.:

AF XY:

0.289

AC XY:

21492

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.276

AC:

11474

AN:

41518

American (AMR)

AF:

0.227

AC:

3478

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.209

AC:

725

AN:

3470

East Asian (EAS)

AF:

0.153

AC:

790

AN:

5166

South Asian (SAS)

AF:

0.242

AC:

1167

AN:

4828

European-Finnish (FIN)

AF:

0.274

AC:

2897

AN:

10586

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.347

AC:

23602

AN:

67962

Other (OTH)

AF:

0.303

AC:

641

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1671

3342

5014

6685

8356

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

468

936

1404

1872

2340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.322

Hom.:

11242

Bravo

AF:

0.294

Asia WGS

AF:

0.229

AC:

799

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 19, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.8

(source)

DANN

Benign

0.55

PhyloP100

-0.083

PromoterAI

-0.0038

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over