1-109690472-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000561.4(GSTM1):c.475C>G(p.Leu159Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 21 hom., cov: 13)

Exomes 𝑓: 0.00016 ( 31 hom. )

Consequence

GSTM1
NM_000561.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0680

Publications

1 publications found

Variant links:

Genes affected

GSTM1 (HGNC:4632): (glutathione S-transferase mu 1) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. Null mutations of this class mu gene have been linked with an increase in a number of cancers, likely due to an increased susceptibility to environmental toxins and carcinogens. Multiple protein isoforms are encoded by transcript variants of this gene. [provided by RefSeq, Jul 2008]

GSTM1 links:

GSTM2 (HGNC:4634): (glutathione S-transferase mu 2) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. [provided by RefSeq, Jul 2008]

GSTM2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008644879).

BP6

Variant 1-109690472-C-G is Benign according to our data. Variant chr1-109690472-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 741106.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000561.4. 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
	GSTM1	NM_000561.4	MANE Select	c.475C>G	p.Leu159Val	missense	Exon 7 of 8	NP_000552.2
	GSTM1	NM_146421.3		c.456+106C>G		intron	N/A	NP_666533.1	X5D932

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GSTM1	ENST00000309851.10	TSL:1 MANE Select	c.475C>G	p.Leu159Val	missense	Exon 7 of 8	ENSP00000311469.5	P09488-1
GSTM1	ENST00000349334.7	TSL:1	c.456+106C>G		intron	N/A	ENSP00000234981.4	P09488-2
GSTM1	ENST00000369819.2	TSL:1	c.360+1147C>G		intron	N/A	ENSP00000358834.2	B9ZVX7

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

AN:

81514

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00268

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000784

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00694

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00189

GnomAD2 exomes

AF:

0.000316

AC:

AN:

135878

AF XY:

0.000178

show subpopulations

Gnomad AFR exome

AF:

0.00336

Gnomad AMR exome

AF:

0.000100

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000156

AC:

112

AN:

716614

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

358418

show subpopulations

African (AFR)

AF:

0.00323

AC:

AN:

24488

American (AMR)

AF:

0.000117

AC:

AN:

25688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13410

East Asian (EAS)

AF:

0.00

AC:

AN:

18046

South Asian (SAS)

AF:

0.0000385

AC:

AN:

51890

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29102

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2564

European-Non Finnish (NFE)

AF:

0.0000211

AC:

AN:

521362

Other (OTH)

AF:

0.000565

AC:

AN:

30064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00105

AC:

AN:

81628

Hom.:

Cov.:

AF XY:

0.000855

AC XY:

AN XY:

39782

show subpopulations

African (AFR)

AF:

0.00267

AC:

AN:

28820

American (AMR)

AF:

0.000782

AC:

AN:

7674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1782

East Asian (EAS)

AF:

0.00

AC:

AN:

2168

South Asian (SAS)

AF:

0.00

AC:

AN:

2720

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5362

Middle Eastern (MID)

AF:

0.00746

AC:

AN:

134

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

31562

Other (OTH)

AF:

0.00189

AC:

AN:

1060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000736

Hom.:

ESP6500AA

AF:

0.00372

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000463

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.050

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.84

M_CAP

Benign

0.0031

MetaRNN

Benign

0.0086

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.3

PhyloP100

0.068

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.4

REVEL

Benign

0.032

Sift

Benign

0.19

Sift4G

Benign

0.29

Polyphen

0.052

Vest4

0.41

MVP

0.21

MPC

1.1

ClinPred

0.012

GERP RS

-1.4

Varity_R

0.26

gMVP

0.52

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over