Genetic Variant NM_000852.4:c.-219C>G (chr11-67583625-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000852.4(GSTP1):c.-219C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0175 in 401,104 control chromosomes in the GnomAD database, including 642 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.027 ( 377 hom., cov: 33)

Exomes 𝑓: 0.012 ( 265 hom. )

Consequence

GSTP1
NM_000852.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.860

Publications

6 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTP1	NM_000852.4 link	c.-219C>G		upstream_gene_variant		ENST00000398606.10	NP_000843.1	P09211V9HWE9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
GSTP1	ENST00000398606.10 link	c.-219C>G	upstream_gene_variant	1	NM_000852.4	ENSP00000381607.3	P09211
GSTP1	ENST00000398603.6 link	c.-219C>G	upstream_gene_variant	3		ENSP00000381604.1	A8MX94
GSTP1	ENST00000494593.1 link	n.-197C>G	upstream_gene_variant	2
GSTP1	ENST00000646888.1 link	n.-219C>G	upstream_gene_variant			ENSP00000494477.1	A0A2R8Y5E5

Frequencies

GnomAD3 genomes

AF:

0.0265

AC:

4035

AN:

152072

Hom.:

375

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0199

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.0259

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.00326

Gnomad OTH

AF:

0.0244

GnomAD4 exome

AF:

0.0119

AC:

2966

AN:

248924

Hom.:

265

Cov.:

AF XY:

0.0113

AC XY:

1435

AN XY:

127234

show subpopulations

African (AFR)

AF:

0.0179

AC:

116

AN:

6468

American (AMR)

AF:

0.239

AC:

1633

AN:

6822

Ashkenazi Jewish (ASJ)

AF:

0.00725

AC:

AN:

8692

East Asian (EAS)

AF:

0.00874

AC:

187

AN:

21394

South Asian (SAS)

AF:

0.000324

AC:

AN:

6170

European-Finnish (FIN)

AF:

0.00109

AC:

AN:

21948

Middle Eastern (MID)

AF:

0.000796

AC:

AN:

1256

European-Non Finnish (NFE)

AF:

0.00360

AC:

576

AN:

160148

Other (OTH)

AF:

0.0227

AC:

364

AN:

16026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

106

212

318

424

530

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0265

AC:

4040

AN:

152180

Hom.:

377

Cov.:

AF XY:

0.0292

AC XY:

2171

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0199

AC:

825

AN:

41552

American (AMR)

AF:

0.181

AC:

2766

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00778

AC:

AN:

3472

East Asian (EAS)

AF:

0.0260

AC:

134

AN:

5160

South Asian (SAS)

AF:

0.00166

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000378

AC:

AN:

10578

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00327

AC:

222

AN:

67984

Other (OTH)

AF:

0.0242

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

173

346

518

691

864

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.00120

Hom.:

Bravo

AF:

0.0436

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.2

(source)

DANN

Benign

0.74

PhyloP100

-0.86

PromoterAI

-0.46

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over