6-1783862-A-G

Position:

• chr6-1783862-A-G

Variant summary

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

The NM_001500.4(GMDS):​c.772-41276T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,884 control chromosomes in the GnomAD database, including 15,183 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 0.44 (15183 hom., cov: 31)
• Consequence: GMDS NM_001500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.649

Genes affected

GMDS (HGNC:4369): (GDP-mannose 4,6-dehydratase) GDP-mannose 4,6-dehydratase (GMD; EC 4.2.1.47) catalyzes the conversion of GDP-mannose to GDP-4-keto-6-deoxymannose, the first step in the synthesis of GDP-fucose from GDP-mannose, using NADP+ as a cofactor. The second and third steps of the pathway are catalyzed by a single enzyme, GDP-keto-6-deoxymannose 3,5-epimerase, 4-reductase, designated FX in humans (MIM 137020).[supplied by OMIM, Aug 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GMDS	NM_001500.4	c.772-41276T>C		intron_variant		ENST00000380815.5	NP_001491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GMDS	ENST00000380815.5	c.772-41276T>C		intron_variant		1	NM_001500.4	ENSP00000370194.4
GMDS	ENST00000530927.5	c.682-41276T>C		intron_variant		1		ENSP00000436726.1
GMDS	ENST00000380805.6	n.898-41276T>C		intron_variant		2
GMDS	ENST00000531690.5	n.251-41276T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67006 AN: 151766 Hom.: 15160 Cov.: 31

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.442 AC: 67066 AN: 151884 Hom.: 15183 Cov.: 31 AF XY: 0.447 AC XY: 33157 AN XY: 74212

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.497

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.421

Alfa AF: 0.401 Hom.: 26272

Bravo AF: 0.434

Asia WGS AF: 0.619 AC: 2151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.5
DANN	Benign	0.46

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: rs6919059; hg19: chr6-1784096;