6-38681018-A-G

Position:

• chr6-38681018-A-G

Variant summary

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

The NM_006708.3(GLO1):​c.466+994T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 152,174 control chromosomes in the GnomAD database, including 58,232 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 0.87 (58232 hom., cov: 32)
• Consequence: GLO1 NM_006708.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLO1	NM_006708.3	c.466+994T>C		intron_variant		ENST00000373365.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLO1	ENST00000373365.5	c.466+994T>C		intron_variant		1	NM_006708.3	P1
GLO1	ENST00000470973.1	n.498+994T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.872 AC: 132554 AN: 152056 Hom.: 58173 Cov.: 32

Gnomad AFR AF: 0.959

Gnomad AMI AF: 0.923

Gnomad AMR AF: 0.877

Gnomad ASJ AF: 0.871

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.894

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.848

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

GnomAD4 genome AF: 0.872 AC: 132674 AN: 152174 Hom.: 58232 Cov.: 32 AF XY: 0.867 AC XY: 64490 AN XY: 74396

Gnomad4 AFR AF: 0.959

Gnomad4 AMR AF: 0.877

Gnomad4 ASJ AF: 0.871

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.894

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.853

Gnomad4 OTH AF: 0.850

Alfa AF: 0.861 Hom.: 38981

Bravo AF: 0.882

Asia WGS AF: 0.807 AC: 2805 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.12
DANN	Benign	0.35

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: rs2736655; hg19: chr6-38648794;