Genetic Variant NM_000852.4:c.232+13C>A (chr11-67584785-C-A) – 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.232+13C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,586,772 control chromosomes in the GnomAD database, including 134,514 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11286 hom., cov: 33)

Exomes 𝑓: 0.41 ( 123228 hom. )

Consequence

GSTP1
NM_000852.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0150

Publications

39 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 11-67584785-C-A is Benign according to our data. Variant chr11-67584785-C-A is described in ClinVar as Benign. ClinVar VariationId is 1297979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.425 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTP1	NM_000852.4	MANE Select	c.232+13C>A		intron	N/A	NP_000843.1	P09211

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GSTP1	ENST00000398606.10	TSL:1 MANE Select	c.232+13C>A	intron	N/A	ENSP00000381607.3	P09211
GSTP1	ENST00000495996.2	TSL:2	c.232+13C>A	intron	N/A	ENSP00000484686.2
GSTP1	ENST00000906565.1		c.232+13C>A	intron	N/A	ENSP00000576624.1

Frequencies

GnomAD3 genomes

AF:

0.377

AC:

57339

AN:

151892

Hom.:

11284

Cov.:

show subpopulations

Gnomad AFR

AF:

0.391

Gnomad AMI

AF:

0.415

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.260

Gnomad EAS

AF:

0.157

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.319

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.429

Gnomad OTH

AF:

0.375

GnomAD2 exomes

AF:

0.343

AC:

84038

AN:

245268

AF XY:

0.349

show subpopulations

Gnomad AFR exome

AF:

0.395

Gnomad AMR exome

AF:

0.219

Gnomad ASJ exome

AF:

0.255

Gnomad EAS exome

AF:

0.156

Gnomad FIN exome

AF:

0.333

Gnomad NFE exome

AF:

0.421

Gnomad OTH exome

AF:

0.367

GnomAD4 exome

AF:

0.407

AC:

583959

AN:

1434762

Hom.:

123228

Cov.:

AF XY:

0.405

AC XY:

289469

AN XY:

715478

show subpopulations

African (AFR)

AF:

0.390

AC:

12828

AN:

32916

American (AMR)

AF:

0.225

AC:

10066

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.259

AC:

6726

AN:

25970

East Asian (EAS)

AF:

0.154

AC:

6079

AN:

39564

South Asian (SAS)

AF:

0.316

AC:

27103

AN:

85760

European-Finnish (FIN)

AF:

0.341

AC:

17964

AN:

52728

Middle Eastern (MID)

AF:

0.373

AC:

2133

AN:

5718

European-Non Finnish (NFE)

AF:

0.439

AC:

478015

AN:

1087928

Other (OTH)

AF:

0.387

AC:

23045

AN:

59494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

16380

32761

49141

65522

81902

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14156

28312

42468

56624

70780

<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:

0.377

AC:

57364

AN:

152010

Hom.:

11286

Cov.:

AF XY:

0.366

AC XY:

27206

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.391

AC:

16198

AN:

41472

American (AMR)

AF:

0.277

AC:

4231

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.260

AC:

901

AN:

3466

East Asian (EAS)

AF:

0.156

AC:

808

AN:

5170

South Asian (SAS)

AF:

0.295

AC:

1423

AN:

4816

European-Finnish (FIN)

AF:

0.319

AC:

3375

AN:

10582

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.429

AC:

29170

AN:

67920

Other (OTH)

AF:

0.372

AC:

785

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

1744

3488

5232

6976

8720

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

564

1128

1692

2256

2820

<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:

0.353

Hom.:

3945

Bravo

AF:

0.375

Asia WGS

AF:

0.254

AC:

887

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.7

(source)

DANN

Benign

0.71

PhyloP100

0.015

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over