1-109656105-C-G

Variant names:

• chr1-109656105-C-G
• rs1010167
• NM_000850.5:c.-285C>G

Variant summary

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

The NM_000850.5(GSTM4):​c.-285C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 430,534 control chromosomes in the GnomAD database, including 38,690 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 0.39 (12493 hom., cov: 32)
  • Exomes 𝑓: 0.42 (26197 hom.)
• Consequence: GSTM4 NM_000850.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102
• Publications: 47 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]

ENSG00000310168 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTM4	NM_000850.5	c.-285C>G		5_prime_UTR_variant	Exon 1 of 8	ENST00000369836.9	NP_000841.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTM4	ENST00000369836.9	c.-285C>G		5_prime_UTR_variant	Exon 1 of 8	1	NM_000850.5	ENSP00000358851.4

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59603 AN: 151956 Hom.: 12483 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.434

GnomAD4 exome AF: 0.422 AC: 117578 AN: 278460 Hom.: 26197 Cov.: 0 AF XY: 0.416 AC XY: 62444 AN XY: 150202

African (AFR) AF: 0.268 AC: 2092 AN: 7800

American (AMR) AF: 0.612 AC: 7655 AN: 12502

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 3486 AN: 7690

East Asian (EAS) AF: 0.702 AC: 10746 AN: 15314

South Asian (SAS) AF: 0.346 AC: 14352 AN: 41536

European-Finnish (FIN) AF: 0.480 AC: 6900 AN: 14380

Middle Eastern (MID) AF: 0.485 AC: 546 AN: 1126

European-Non Finnish (NFE) AF: 0.400 AC: 65314 AN: 163152

Other (OTH) AF: 0.434 AC: 6487 AN: 14960

GnomAD4 genome AF: 0.392 AC: 59635 AN: 152074 Hom.: 12493 Cov.: 32 AF XY: 0.398 AC XY: 29606 AN XY: 74344

African (AFR) AF: 0.280 AC: 11634 AN: 41490

American (AMR) AF: 0.546 AC: 8352 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1579 AN: 3468

East Asian (EAS) AF: 0.663 AC: 3413 AN: 5148

South Asian (SAS) AF: 0.335 AC: 1618 AN: 4830

European-Finnish (FIN) AF: 0.472 AC: 4994 AN: 10578

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26859 AN: 67958

Other (OTH) AF: 0.437 AC: 923 AN: 2114

Alfa AF: 0.387 Hom.: 1460

Bravo AF: 0.398

Asia WGS AF: 0.497 AC: 1726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	6.8
DANN	Benign	0.64
PhyloP100		-0.10
PromoterAI		-0.56	Under-expression
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1010167; hg19: chr1-110198727;