chr1-109687322-G-C

Variant names:

• chr1-109687322-G-C
• rs412543
• ENST00000369831.6:c.567+15739G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000369831.6(GSTM2):​c.567+15739G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.82 (25229 hom., cov: 9)
• Consequence: GSTM2 ENST00000369831.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.76
• Publications: 19 publications found

Genes affected

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BS2: High Homozygotes in GnomAd4 at 25229 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000369831.6. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM2	ENST00000369831.6	TSL:2	c.567+15739G>C		intron	N/A	ENSP00000358846.2
	GSTM2	ENST00000460717.8	TSL:2	c.*17+5488G>C		intron	N/A	ENSP00000435910.2

Frequencies

GnomAD3 genomes AF: 0.820 AC: 55741 AN: 68006 Hom.: 25198 Cov.: 9

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.937

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.852

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.819 AC: 55812 AN: 68108 Hom.: 25229 Cov.: 9 AF XY: 0.816 AC XY: 26713 AN XY: 32732

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.667 AC: 14523 AN: 21784

American (AMR) AF: 0.915 AC: 5741 AN: 6274

Ashkenazi Jewish (ASJ) AF: 0.915 AC: 1480 AN: 1618

East Asian (EAS) AF: 0.910 AC: 1680 AN: 1846

South Asian (SAS) AF: 0.937 AC: 1949 AN: 2080

European-Finnish (FIN) AF: 0.748 AC: 3122 AN: 4172

Middle Eastern (MID) AF: 0.952 AC: 99 AN: 104

European-Non Finnish (NFE) AF: 0.905 AC: 26337 AN: 29098

Other (OTH) AF: 0.855 AC: 703 AN: 822

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.087
DANN	Benign	0.62
PhyloP100		-2.8
PromoterAI		-0.016	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs412543; hg19: chr1-110229944; COSMIC: COSV59166678; COSMIC: COSV59166678;