1-109658958-C-T

Variant names:

• chr1-109658958-C-T
• rs650985
• NM_000850.5:c.457-42C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• Publications: 21 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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	c.457-42C>T		intron_variant	Intron 6 of 7	ENST00000369836.9	NP_000841.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.961 AC: 146225 AN: 152232 Hom.: 70250 Cov.: 33

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

GnomAD2 exomes AF: 0.960 AC: 241317 AN: 251484 AF XY: 0.959

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 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.: 38 AF XY: 0.946 AC XY: 687210 AN XY: 726668

African (AFR) AF: 0.988 AC: 33048 AN: 33450

American (AMR) AF: 0.973 AC: 43535 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.946 AC: 24727 AN: 26132

East Asian (EAS) AF: 1.00 AC: 39691 AN: 39696

South Asian (SAS) AF: 0.981 AC: 84554 AN: 86218

European-Finnish (FIN) AF: 0.962 AC: 51379 AN: 53420

Middle Eastern (MID) AF: 0.975 AC: 5626 AN: 5768

European-Non Finnish (NFE) AF: 0.936 AC: 1039949 AN: 1110856

Other (OTH) AF: 0.952 AC: 57479 AN: 60352

GnomAD4 genome AF: 0.961 AC: 146345 AN: 152350 Hom.: 70311 Cov.: 33 AF XY: 0.962 AC XY: 71678 AN XY: 74496

African (AFR) AF: 0.986 AC: 40985 AN: 41578

American (AMR) AF: 0.968 AC: 14821 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.945 AC: 3280 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5180 AN: 5180

South Asian (SAS) AF: 0.982 AC: 4742 AN: 4830

European-Finnish (FIN) AF: 0.963 AC: 10230 AN: 10628

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.940 AC: 63985 AN: 68034

Other (OTH) AF: 0.966 AC: 2044 AN: 2116

Alfa AF: 0.946 Hom.: 131685

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
PhyloP100		0.049
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs650985; hg19: chr1-110201580;