chr6-1757945-T-C

Variant names:

• chr6-1757945-T-C
• rs1040530
• NM_001500.4:c.772-15359A>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.772-15359A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 152,144 control chromosomes in the GnomAD database, including 23,780 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 0.55 (23780 hom., cov: 34)
• Consequence: GMDS NM_001500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 1 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]

LOC124901239 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GMDS	NM_001500.4	c.772-15359A>G		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.772-15359A>G		intron_variant	Intron 7 of 10	1	NM_001500.4	ENSP00000370194.4
GMDS	ENST00000530927.5	c.682-15359A>G		intron_variant	Intron 7 of 10	1		ENSP00000436726.1
GMDS	ENST00000380805.6	n.898-15359A>G		intron_variant	Intron 1 of 5	2
GMDS	ENST00000531690.5	n.251-15359A>G		intron_variant	Intron 3 of 5	5

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83894 AN: 152026 Hom.: 23749 Cov.: 34

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.552 AC: 83970 AN: 152144 Hom.: 23780 Cov.: 34 AF XY: 0.540 AC XY: 40139 AN XY: 74366

African (AFR) AF: 0.668 AC: 27721 AN: 41510

American (AMR) AF: 0.563 AC: 8610 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1897 AN: 3470

East Asian (EAS) AF: 0.350 AC: 1813 AN: 5180

South Asian (SAS) AF: 0.411 AC: 1981 AN: 4824

European-Finnish (FIN) AF: 0.372 AC: 3937 AN: 10582

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.534 AC: 36269 AN: 67970

Other (OTH) AF: 0.552 AC: 1165 AN: 2112

Alfa AF: 0.535 Hom.: 11244

Bravo AF: 0.571

Asia WGS AF: 0.386 AC: 1344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.19
DANN	Benign	0.70
PhyloP100		-1.9
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: rs1040530; hg19: chr6-1758179; COSMIC: COSV66415648;