1-109659077-T-C

Variant names:

• chr1-109659077-T-C
• rs506008
• NM_000850.5:c.534T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000850.5(GSTM4):​c.534T>C​(p.Phe178Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 1,614,000 control chromosomes in the GnomAD database, including 599,512 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 0.80 (50007 hom., cov: 32)
  • Exomes 𝑓: 0.87 (549505 hom.)
• Consequence: GSTM4 NM_000850.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181
• Publications: 30 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=0.181 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000850.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM4	NM_000850.5	MANE Select	c.534T>C	p.Phe178Phe	synonymous	Exon 7 of 8	NP_000841.1
	GSTM4	NM_147148.3		c.534T>C	p.Phe178Phe	synonymous	Exon 7 of 8	NP_671489.1
	GSTM4	NR_024538.2		n.743T>C		non_coding_transcript_exon	Exon 6 of 7

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM4	ENST00000369836.9	TSL:1 MANE Select	c.534T>C	p.Phe178Phe	synonymous	Exon 7 of 8	ENSP00000358851.4
	GSTM4	ENST00000326729.9	TSL:1	c.534T>C	p.Phe178Phe	synonymous	Exon 7 of 8	ENSP00000316471.5
	GSTM4	ENST00000495742.5	TSL:1	n.590T>C		non_coding_transcript_exon	Exon 6 of 7

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121815 AN: 152020 Hom.: 49990 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.828

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.870

Gnomad OTH AF: 0.822

GnomAD2 exomes AF: 0.868 AC: 218229 AN: 251494 AF XY: 0.871

Gnomad AFR exome AF: 0.593

Gnomad AMR exome AF: 0.921

Gnomad ASJ exome AF: 0.858

Gnomad EAS exome AF: 0.978

Gnomad FIN exome AF: 0.885

Gnomad NFE exome AF: 0.869

Gnomad OTH exome AF: 0.869

GnomAD4 exome AF: 0.866 AC: 1265423 AN: 1461862 Hom.: 549505 Cov.: 86 AF XY: 0.866 AC XY: 629959 AN XY: 727230

African (AFR) AF: 0.583 AC: 19525 AN: 33480

American (AMR) AF: 0.915 AC: 40901 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 22399 AN: 26134

East Asian (EAS) AF: 0.967 AC: 38383 AN: 39700

South Asian (SAS) AF: 0.873 AC: 75310 AN: 86258

European-Finnish (FIN) AF: 0.890 AC: 47523 AN: 53420

Middle Eastern (MID) AF: 0.839 AC: 4837 AN: 5768

European-Non Finnish (NFE) AF: 0.868 AC: 964777 AN: 1111984

Other (OTH) AF: 0.857 AC: 51768 AN: 60394

GnomAD4 genome AF: 0.801 AC: 121868 AN: 152138 Hom.: 50007 Cov.: 32 AF XY: 0.805 AC XY: 59886 AN XY: 74378

African (AFR) AF: 0.603 AC: 24991 AN: 41456

American (AMR) AF: 0.870 AC: 13304 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.862 AC: 2992 AN: 3470

East Asian (EAS) AF: 0.972 AC: 5012 AN: 5154

South Asian (SAS) AF: 0.872 AC: 4205 AN: 4822

European-Finnish (FIN) AF: 0.891 AC: 9447 AN: 10608

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.870 AC: 59187 AN: 68012

Other (OTH) AF: 0.823 AC: 1740 AN: 2114

Alfa AF: 0.837 Hom.: 21172

Bravo AF: 0.792

Asia WGS AF: 0.894 AC: 3107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.2
DANN	Benign	0.46
PhyloP100		0.18
Mutation Taster		=100/0	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: rs506008; hg19: chr1-110201699; COSMIC: COSV58694178; COSMIC: COSV58694178;