rs2761233

Variant names:

• chr6-1948867-T-C
• rs2761233
• NM_001500.4:c.643+11000A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001500.4(GMDS):​c.643+11000A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,132 control chromosomes in the GnomAD database, including 6,042 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 0.25 (6042 hom., cov: 32)
• Consequence: GMDS NM_001500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GMDS	NM_001500.4	c.643+11000A>G		intron_variant	Intron 6 of 10	ENST00000380815.5	NP_001491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GMDS	ENST00000380815.5	c.643+11000A>G		intron_variant	Intron 6 of 10	1	NM_001500.4	ENSP00000370194.4
GMDS	ENST00000530927.5	c.553+11000A>G		intron_variant	Intron 6 of 10	1		ENSP00000436726.1
GMDS	ENST00000530459.1	n.396+11000A>G		intron_variant	Intron 3 of 3	3
GMDS	ENST00000531690.5	n.122+11000A>G		intron_variant	Intron 2 of 5	5

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37373 AN: 152014 Hom.: 6005 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.246 AC: 37462 AN: 152132 Hom.: 6042 Cov.: 32 AF XY: 0.248 AC XY: 18439 AN XY: 74384

African (AFR) AF: 0.462 AC: 19148 AN: 41484

American (AMR) AF: 0.214 AC: 3276 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 418 AN: 3468

East Asian (EAS) AF: 0.199 AC: 1029 AN: 5176

South Asian (SAS) AF: 0.131 AC: 631 AN: 4818

European-Finnish (FIN) AF: 0.218 AC: 2305 AN: 10584

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10072 AN: 68002

Other (OTH) AF: 0.207 AC: 435 AN: 2106

Alfa AF: 0.174 Hom.: 3155

Bravo AF: 0.250

Asia WGS AF: 0.177 AC: 616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.6
DANN	Benign	0.66
PhyloP100		0.027
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2761233; hg19: chr6-1949101;