rs1130534

Variant names:

• chr6-38682812-T-A
• rs1130534
• NM_006708.3:c.372A>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_006708.3(GLO1):​c.372A>T​(p.Gly124Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,575,686 control chromosomes in the GnomAD database, including 16,596 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 0.18 (3112 hom., cov: 32)
  • Exomes 𝑓: 0.12 (13484 hom.)
• Consequence: GLO1 NM_006708.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291
• Publications: 30 publications found

Genes affected

GLO1 (HGNC:4323): (glyoxalase I) The enzyme encoded by this gene is responsible for the catalysis and formation of S-lactoyl-glutathione from methylglyoxal condensation and reduced glutatione. Glyoxalase I is linked to HLA and is localized to 6p21.3-p21.1, between HLA and the centromere. [provided by RefSeq, Jul 2008]

ENSG00000298390 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=0.291 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006708.3. 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
	GLO1	NM_006708.3	MANE Select	c.372A>T	p.Gly124Gly	synonymous	Exon 4 of 6	NP_006699.2	Q04760-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLO1	ENST00000373365.5	TSL:1 MANE Select	c.372A>T	p.Gly124Gly	synonymous	Exon 4 of 6	ENSP00000362463.3	Q04760-1
	GLO1	ENST00000887179.1		c.405A>T	p.Gly135Gly	synonymous	Exon 5 of 7	ENSP00000557238.1
	GLO1	ENST00000887178.1		c.372A>T	p.Gly124Gly	synonymous	Exon 4 of 6	ENSP00000557237.1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27537 AN: 151920 Hom.: 3111 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.0884

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.173

GnomAD2 exomes AF: 0.159 AC: 39850 AN: 251310 AF XY: 0.161

Gnomad AFR exome AF: 0.314

Gnomad AMR exome AF: 0.134

Gnomad ASJ exome AF: 0.230

Gnomad EAS exome AF: 0.237

Gnomad FIN exome AF: 0.0851

Gnomad NFE exome AF: 0.115

Gnomad OTH exome AF: 0.148

GnomAD4 exome AF: 0.125 AC: 177800 AN: 1423648 Hom.: 13484 Cov.: 25 AF XY: 0.129 AC XY: 91428 AN XY: 710958

African (AFR) AF: 0.317 AC: 10356 AN: 32626

American (AMR) AF: 0.138 AC: 6145 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 5968 AN: 25860

East Asian (EAS) AF: 0.205 AC: 8076 AN: 39470

South Asian (SAS) AF: 0.249 AC: 21258 AN: 85384

European-Finnish (FIN) AF: 0.0882 AC: 4706 AN: 53386

Middle Eastern (MID) AF: 0.226 AC: 1288 AN: 5700

European-Non Finnish (NFE) AF: 0.103 AC: 111378 AN: 1077478

Other (OTH) AF: 0.146 AC: 8625 AN: 59078

GnomAD4 genome AF: 0.181 AC: 27559 AN: 152038 Hom.: 3112 Cov.: 32 AF XY: 0.182 AC XY: 13530 AN XY: 74328

African (AFR) AF: 0.308 AC: 12761 AN: 41402

American (AMR) AF: 0.157 AC: 2401 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 812 AN: 3468

East Asian (EAS) AF: 0.231 AC: 1198 AN: 5178

South Asian (SAS) AF: 0.243 AC: 1173 AN: 4820

European-Finnish (FIN) AF: 0.0884 AC: 935 AN: 10580

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7771 AN: 68008

Other (OTH) AF: 0.171 AC: 361 AN: 2106

Alfa AF: 0.144 Hom.: 622

Bravo AF: 0.190

Asia WGS AF: 0.217 AC: 751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	7.0
DANN	Benign	0.57
PhyloP100		0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	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: rs1130534; hg19: chr6-38650588; COSMIC: COSV64905133;