rs1049346

chr6-38703061-G-Achr6-38703061-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006708.3(GLO1):c.-7C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 1,517,806 control chromosomes in the GnomAD database, including 181,471 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 0.54 (22719 hom., cov: 33)
  • Exomes 𝑓: 0.48 (158752 hom.)
• Consequence: GLO1 NM_006708.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.632

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLO1	NM_006708.3	c.-7C>T		5_prime_UTR_variant	1/6	ENST00000373365.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLO1	ENST00000373365.5	c.-7C>T		5_prime_UTR_variant	1/6	1	NM_006708.3	P1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81834 AN: 152002 Hom.: 22696 Cov.: 33

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.511

GnomAD3 exomes AF: 0.495 AC: 115352 AN: 233028 Hom.: 28977 AF XY: 0.494 AC XY: 63239 AN XY: 128100

Gnomad AFR exome AF: 0.677

Gnomad AMR exome AF: 0.445

Gnomad ASJ exome AF: 0.490

Gnomad EAS exome AF: 0.622

Gnomad SAS exome AF: 0.518

Gnomad FIN exome AF: 0.390

Gnomad NFE exome AF: 0.480

Gnomad OTH exome AF: 0.486

GnomAD4 exome AF: 0.479 AC: 653923 AN: 1365686 Hom.: 158752 Cov.: 23 AF XY: 0.480 AC XY: 328235 AN XY: 684302

Gnomad4 AFR exome AF: 0.674

Gnomad4 AMR exome AF: 0.455

Gnomad4 ASJ exome AF: 0.489

Gnomad4 EAS exome AF: 0.580

Gnomad4 SAS exome AF: 0.511

Gnomad4 FIN exome AF: 0.401

Gnomad4 NFE exome AF: 0.470

Gnomad4 OTH exome AF: 0.495

GnomAD4 genome AF: 0.538 AC: 81907 AN: 152120 Hom.: 22719 Cov.: 33 AF XY: 0.533 AC XY: 39634 AN XY: 74362

Gnomad4 AFR AF: 0.675

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.511

Alfa AF: 0.496 Hom.: 37290

Bravo AF: 0.551

Asia WGS AF: 0.538 AC: 1870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	3.2
Dann	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1049346; hg19: chr6-38670837; COSMIC: COSV64905834;