Genetic Variant GSTM4:c.457-42C>T (chr1-109658958-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000850.5(GSTM4):c.457-42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.946 in 1,612,966 control chromosomes in the GnomAD database, including 722,469 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 0.96 ( 70311 hom., cov: 33)

Exomes 𝑓: 0.94 ( 652158 hom. )

Consequence

GSTM4
NM_000850.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0490

Variant links:

Genes affected

GSTM4 (HGNC:4636): (glutathione S-transferase mu 4) 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. Diversification of these genes has occurred in regions encoding substrate-binding domains, as well as in tissue expression patterns, to accommodate an increasing number of foreign compounds. Multiple transcript variants, each encoding a distinct protein isoform, have been identified. [provided by RefSeq, Jul 2008]

GSTM4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTM4	NM_000850.5 link	c.457-42C>T		intron_variant	Intron 6 of 7	ENST00000369836.9	NP_000841.1	Q03013-1A0A140VKE3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTM4	ENST00000369836.9 link	c.457-42C>T		intron_variant	Intron 6 of 7	1	NM_000850.5	ENSP00000358851.4		Q03013-1

Frequencies

GnomAD3 genomes

AF:

0.961

AC:

146225

AN:

152232

Hom.:

70250

Cov.:

show subpopulations

Gnomad AFR

AF:

0.986

Gnomad AMI

AF:

0.868

Gnomad AMR

AF:

0.968

Gnomad ASJ

AF:

0.945

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.982

Gnomad FIN

AF:

0.963

Gnomad MID

AF:

0.968

Gnomad NFE

AF:

0.940

Gnomad OTH

AF:

0.966

GnomAD3 exomes

AF:

0.960

AC:

241317

AN:

251484

Hom.:

115834

AF XY:

0.959

AC XY:

130370

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.988

Gnomad AMR exome

AF:

0.975

Gnomad ASJ exome

AF:

0.944

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.981

Gnomad FIN exome

AF:

0.961

Gnomad NFE exome

AF:

0.940

Gnomad OTH exome

AF:

0.951

GnomAD4 exome

AF:

0.945

AC:

1379988

AN:

1460616

Hom.:

652158

Cov.:

AF XY:

0.946

AC XY:

687210

AN XY:

726668

show subpopulations

Gnomad4 AFR exome

AF:

0.988

Gnomad4 AMR exome

AF:

0.973

Gnomad4 ASJ exome

AF:

0.946

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.981

Gnomad4 FIN exome

AF:

0.962

Gnomad4 NFE exome

AF:

0.936

Gnomad4 OTH exome

AF:

0.952

GnomAD4 genome

AF:

0.961

AC:

146345

AN:

152350

Hom.:

70311

Cov.:

AF XY:

0.962

AC XY:

71678

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.986

Gnomad4 AMR

AF:

0.968

Gnomad4 ASJ

AF:

0.945

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.982

Gnomad4 FIN

AF:

0.963

Gnomad4 NFE

AF:

0.940

Gnomad4 OTH

AF:

0.966

Alfa

AF:

0.946

Hom.:

101720

Bravo

AF:

0.962

Asia WGS

AF:

0.991

AC:

3445

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.6

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over