chr1-109657738-T-C

Variant names:

• chr1-109657738-T-C
• rs560018
• NM_000850.5:c.260-34T>C

Variant summary

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

The NM_000850.5(GSTM4):​c.260-34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 1,613,966 control chromosomes in the GnomAD database, including 90,313 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 0.26 (6109 hom., cov: 32)
  • Exomes 𝑓: 0.33 (84204 hom.)
• Consequence: GSTM4 NM_000850.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.30
• Publications: 32 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.361 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM4	NM_000850.5	MANE Select	c.260-34T>C		intron	N/A	NP_000841.1	A0A140VKE3
	GSTM4	NM_147148.3		c.260-34T>C		intron	N/A	NP_671489.1	Q03013-2
	GSTM4	NR_024538.2		n.469-34T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM4	ENST00000369836.9	TSL:1 MANE Select	c.260-34T>C		intron	N/A	ENSP00000358851.4	Q03013-1
	GSTM4	ENST00000326729.9	TSL:1	c.260-34T>C		intron	N/A	ENSP00000316471.5	Q03013-2
	GSTM4	ENST00000495742.5	TSL:1	n.316-34T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39595 AN: 152024 Hom.: 6109 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.0464

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.268

GnomAD2 exomes AF: 0.265 AC: 66638 AN: 251444 AF XY: 0.269

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.203

Gnomad ASJ exome AF: 0.325

Gnomad EAS exome AF: 0.0496

Gnomad FIN exome AF: 0.283

Gnomad NFE exome AF: 0.360

Gnomad OTH exome AF: 0.287

GnomAD4 exome AF: 0.328 AC: 479180 AN: 1461824 Hom.: 84204 Cov.: 37 AF XY: 0.324 AC XY: 235381 AN XY: 727212

African (AFR) AF: 0.112 AC: 3748 AN: 33480

American (AMR) AF: 0.207 AC: 9259 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 8467 AN: 26132

East Asian (EAS) AF: 0.0335 AC: 1330 AN: 39700

South Asian (SAS) AF: 0.162 AC: 13936 AN: 86254

European-Finnish (FIN) AF: 0.290 AC: 15518 AN: 53420

Middle Eastern (MID) AF: 0.204 AC: 1177 AN: 5766

European-Non Finnish (NFE) AF: 0.367 AC: 407804 AN: 1111954

Other (OTH) AF: 0.297 AC: 17941 AN: 60394

GnomAD4 genome AF: 0.260 AC: 39595 AN: 152142 Hom.: 6109 Cov.: 32 AF XY: 0.254 AC XY: 18872 AN XY: 74386

African (AFR) AF: 0.121 AC: 5006 AN: 41528

American (AMR) AF: 0.242 AC: 3707 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1132 AN: 3466

East Asian (EAS) AF: 0.0459 AC: 238 AN: 5180

South Asian (SAS) AF: 0.143 AC: 689 AN: 4830

European-Finnish (FIN) AF: 0.286 AC: 3023 AN: 10572

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24773 AN: 67966

Other (OTH) AF: 0.265 AC: 560 AN: 2110

Alfa AF: 0.324 Hom.: 19086

Bravo AF: 0.254

Asia WGS AF: 0.0950 AC: 333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.54
PhyloP100		-3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs560018; hg19: chr1-110200360; COSMIC: COSV58694494; COSMIC: COSV58694494;