rs1130534

Positions:

• chr6-38682812-T-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_006708.3(GLO1):​c.372A>T​(p.Gly124=) 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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLO1	NM_006708.3	c.372A>T	p.Gly124=	synonymous_variant	4/6	ENST00000373365.5	NP_006699.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLO1	ENST00000373365.5	c.372A>T	p.Gly124=	synonymous_variant	4/6	1	NM_006708.3	ENSP00000362463	P1
GLO1	ENST00000470973.1	n.404A>T		non_coding_transcript_exon_variant	1/3	2

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

GnomAD3 exomes AF: 0.159 AC: 39850 AN: 251310 Hom.: 3796 AF XY: 0.161 AC XY: 21815 AN XY: 135832

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 SAS exome AF: 0.250

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

Gnomad4 AFR exome AF: 0.317

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.231

Gnomad4 EAS exome AF: 0.205

Gnomad4 SAS exome AF: 0.249

Gnomad4 FIN exome AF: 0.0882

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.146

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

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.0884

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.171

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	7.0
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs1130534; hg19: chr6-38650588; COSMIC: COSV64905133;