rs7667766

Positions:

• chr4-39502685-C-A
• chr4-39502685-C-G
• chr4-39502685-C-T

Variant summary

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

The NM_003359.4(UGDH):​c.1374+1190G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 152,144 control chromosomes in the GnomAD database, including 31,302 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 0.64 (31302 hom., cov: 32)
• Consequence: UGDH NM_003359.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396

Genes affected

UGDH (HGNC:12525): (UDP-glucose 6-dehydrogenase) The protein encoded by this gene converts UDP-glucose to UDP-glucuronate and thereby participates in the biosynthesis of glycosaminoglycans such as hyaluronan, chondroitin sulfate, and heparan sulfate. These glycosylated compounds are common components of the extracellular matrix and likely play roles in signal transduction, cell migration, and cancer growth and metastasis. The expression of this gene is up-regulated by transforming growth factor beta and down-regulated by hypoxia. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGDH	NM_003359.4	c.1374+1190G>T		intron_variant		ENST00000316423.11	NP_003350.1
UGDH	NM_001184700.2	c.1173+1190G>T		intron_variant			NP_001171629.1
UGDH	NM_001184701.2	c.1083+1190G>T		intron_variant			NP_001171630.1
UGDH	XM_005262667.4	c.1413+1190G>T		intron_variant			XP_005262724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGDH	ENST00000316423.11	c.1374+1190G>T		intron_variant		1	NM_003359.4	ENSP00000319501	P1
UGDH	ENST00000501493.6	c.1173+1190G>T		intron_variant		2		ENSP00000422909
UGDH	ENST00000506179.5	c.1374+1190G>T		intron_variant		5		ENSP00000421757	P1
UGDH	ENST00000507089.5	c.1083+1190G>T		intron_variant		2		ENSP00000426560

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96940 AN: 152026 Hom.: 31281 Cov.: 32

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.861

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.601

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

GnomAD4 genome AF: 0.638 AC: 96999 AN: 152144 Hom.: 31302 Cov.: 32 AF XY: 0.644 AC XY: 47918 AN XY: 74374

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.700

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.861

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.599

Alfa AF: 0.623 Hom.: 37636

Bravo AF: 0.635

Asia WGS AF: 0.666 AC: 2315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7667766; hg19: chr4-39504305;