rs234937

Variant names:

• chr6-2230018-T-C
• rs234937
• NM_001500.4:c.102+15303A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-2230018-T-C
• chr6-2230018-T-G

Variant summary

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

The NM_001500.4(GMDS):​c.102+15303A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 142,010 control chromosomes in the GnomAD database, including 10,407 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 0.36 (10407 hom., cov: 29)
• Consequence: GMDS NM_001500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46

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]

ENSG00000285603 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GMDS	NM_001500.4	c.102+15303A>G		intron_variant	Intron 1 of 10	ENST00000380815.5	NP_001491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GMDS	ENST00000380815.5	c.102+15303A>G		intron_variant	Intron 1 of 10	1	NM_001500.4	ENSP00000370194.4
ENSG00000285603	ENST00000650019.1	n.565T>C		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.357 AC: 50646 AN: 141914 Hom.: 10394 Cov.: 29

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.520

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.357 AC: 50705 AN: 142010 Hom.: 10407 Cov.: 29 AF XY: 0.355 AC XY: 24625 AN XY: 69430

Gnomad4 AFR AF: 0.621

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.382

Alfa AF: 0.269 Hom.: 5442

Bravo AF: 0.417

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.0
DANN	Benign	0.49

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: rs234937; hg19: chr6-2230252;