chr1-109688178-C-A

Variant names:

• chr1-109688178-C-A
• rs567320393
• NM_000561.4:c.45C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000561.4(GSTM1):​c.45C>A​(p.His15Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (5 hom., cov: 13)
  • Exomes 𝑓: 0.00042 (116 hom.)
• Consequence: GSTM1 NM_000561.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.388
• Publications: 1 publications found

Genes affected

GSTM1 (HGNC:4632): (glutathione S-transferase mu 1) 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. Null mutations of this class mu gene have been linked with an increase in a number of cancers, likely due to an increased susceptibility to environmental toxins and carcinogens. Multiple protein isoforms are encoded by transcript variants of this gene. [provided by RefSeq, Jul 2008]

GSTM2 (HGNC:4634): (glutathione S-transferase mu 2) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0056289732).
• BP6: Variant 1-109688178-C-A is Benign according to our data. Variant chr1-109688178-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 754642.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000561.4. 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
	GSTM1	NM_000561.4	MANE Select	c.45C>A	p.His15Gln	missense	Exon 2 of 8	NP_000552.2
	GSTM1	NM_146421.3		c.45C>A	p.His15Gln	missense	Exon 2 of 7	NP_666533.1	X5D932

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM1	ENST00000309851.10	TSL:1 MANE Select	c.45C>A	p.His15Gln	missense	Exon 2 of 8	ENSP00000311469.5	P09488-1
	GSTM1	ENST00000349334.7	TSL:1	c.45C>A	p.His15Gln	missense	Exon 2 of 7	ENSP00000234981.4	P09488-2
	GSTM1	ENST00000369819.2	TSL:1	c.45C>A	p.His15Gln	missense	Exon 2 of 6	ENSP00000358834.2	B9ZVX7

Frequencies

GnomAD3 genomes AF: 0.000121 AC: 10 AN: 82564 Hom.: 5 Cov.: 13

Gnomad AFR AF: 0.0000688

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00215

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000630

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000921 AC: 122 AN: 132486 AF XY: 0.00117

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000518

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000240

Gnomad OTH exome AF: 0.00128

GnomAD4 exome AF: 0.000415 AC: 297 AN: 715554 Hom.: 116 Cov.: 0 AF XY: 0.000571 AC XY: 204 AN XY: 357504

African (AFR) AF: 0.00 AC: 0 AN: 24528

American (AMR) AF: 0.0000399 AC: 1 AN: 25060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13410

East Asian (EAS) AF: 0.00 AC: 0 AN: 18004

South Asian (SAS) AF: 0.00433 AC: 225 AN: 51910

European-Finnish (FIN) AF: 0.0000691 AC: 2 AN: 28946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2548

European-Non Finnish (NFE) AF: 0.0000806 AC: 42 AN: 521162

Other (OTH) AF: 0.000900 AC: 27 AN: 29986

GnomAD4 genome AF: 0.000121 AC: 10 AN: 82680 Hom.: 5 Cov.: 13 AF XY: 0.000149 AC XY: 6 AN XY: 40382

African (AFR) AF: 0.0000685 AC: 2 AN: 29192

American (AMR) AF: 0.00 AC: 0 AN: 7900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1792

East Asian (EAS) AF: 0.00 AC: 0 AN: 2186

South Asian (SAS) AF: 0.00216 AC: 6 AN: 2782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 134

European-Non Finnish (NFE) AF: 0.0000630 AC: 2 AN: 31728

Other (OTH) AF: 0.00 AC: 0 AN: 1086

Alfa AF: 0.000169 Hom.: 1

ExAC AF: 0.000829 AC: 63

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	18
DANN	Benign	0.88
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.045	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.0056	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.51	N
PhyloP100		-0.39
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.074
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		1.0	D
Vest4		0.45
MutPred		0.58		Gain of MoRF binding (P = 0.0974)
MVP		0.23
MPC		1.4
ClinPred		0.038	T
GERP RS		-4.1
PromoterAI		0.016	Neutral
Varity_R		0.28
gMVP		0.71
Mutation Taster		=94/6	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: rs567320393; hg19: chr1-110230800;