chr4-39516490-T-G

Position:

• chr4-39516490-T-G

Variant summary

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

The NM_003359.4(UGDH):​c.163-2306A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 151,982 control chromosomes in the GnomAD database, including 39,090 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 0.72 (39090 hom., cov: 31)
• Consequence: UGDH NM_003359.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261

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]

UGDH (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGDH	NM_003359.4	c.163-2306A>C		intron_variant		ENST00000316423.11	NP_003350.1
UGDH	NM_001184700.2	c.163-2306A>C		intron_variant			NP_001171629.1
UGDH	NM_001184701.2	c.-129-2306A>C		intron_variant			NP_001171630.1
UGDH	XM_005262667.4	c.202-2306A>C		intron_variant			XP_005262724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGDH	ENST00000316423.11	c.163-2306A>C		intron_variant		1	NM_003359.4	ENSP00000319501.6

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108669 AN: 151864 Hom.: 39049 Cov.: 31

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.716 AC: 108766 AN: 151982 Hom.: 39090 Cov.: 31 AF XY: 0.722 AC XY: 53612 AN XY: 74272

Gnomad4 AFR AF: 0.723

Gnomad4 AMR AF: 0.764

Gnomad4 ASJ AF: 0.702

Gnomad4 EAS AF: 0.905

Gnomad4 SAS AF: 0.734

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.685

Alfa AF: 0.693 Hom.: 74093

Bravo AF: 0.718

Asia WGS AF: 0.804 AC: 2794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.47
DANN	Benign	0.81

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: rs6817264; hg19: chr4-39518110;