rs11969985

Variant names:

• chr6-1922673-G-A
• rs11969985
• NM_001500.4:c.771+7430C>T

Variant summary

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

The NM_001500.4(GMDS):​c.771+7430C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,080 control chromosomes in the GnomAD database, including 2,621 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 0.18 (2621 hom., cov: 32)
• Consequence: GMDS NM_001500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 22 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GMDS	NM_001500.4	c.771+7430C>T		intron_variant	Intron 7 of 10	ENST00000380815.5	NP_001491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GMDS	ENST00000380815.5	c.771+7430C>T		intron_variant	Intron 7 of 10	1	NM_001500.4	ENSP00000370194.4
GMDS	ENST00000530927.5	c.681+7430C>T		intron_variant	Intron 7 of 10	1		ENSP00000436726.1
GMDS	ENST00000380805.6	n.897+7430C>T		intron_variant	Intron 1 of 5	2
GMDS	ENST00000531690.5	n.250+7430C>T		intron_variant	Intron 3 of 5	5

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27434 AN: 151962 Hom.: 2609 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.181 AC: 27487 AN: 152080 Hom.: 2621 Cov.: 32 AF XY: 0.184 AC XY: 13665 AN XY: 74328

African (AFR) AF: 0.234 AC: 9683 AN: 41458

American (AMR) AF: 0.191 AC: 2922 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 414 AN: 3468

East Asian (EAS) AF: 0.197 AC: 1019 AN: 5164

South Asian (SAS) AF: 0.136 AC: 655 AN: 4818

European-Finnish (FIN) AF: 0.216 AC: 2287 AN: 10564

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10033 AN: 68002

Other (OTH) AF: 0.156 AC: 330 AN: 2110

Alfa AF: 0.155 Hom.: 3652

Bravo AF: 0.175

Asia WGS AF: 0.163 AC: 565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.4
DANN	Benign	0.22
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11969985; hg19: chr6-1922907;