rs6817264

Variant names:

• chr4-39516490-T-G
• rs6817264
• NM_003359.4:c.163-2306A>C

Variant summary

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

The ENST00000316423.11(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 ENST00000316423.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261
• Publications: 15 publications found

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 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 84

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000316423.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGDH	NM_003359.4	MANE Select	c.163-2306A>C		intron	N/A	NP_003350.1
	UGDH	NM_001184700.2		c.163-2306A>C		intron	N/A	NP_001171629.1
	UGDH	NM_001184701.2		c.-129-2306A>C		intron	N/A	NP_001171630.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGDH	ENST00000316423.11	TSL:1 MANE Select	c.163-2306A>C		intron	N/A	ENSP00000319501.6
	UGDH	ENST00000506179.5	TSL:5	c.163-2306A>C		intron	N/A	ENSP00000421757.1
	UGDH	ENST00000501493.6	TSL:2	c.163-2306A>C		intron	N/A	ENSP00000422909.1

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

African (AFR) AF: 0.723 AC: 29957 AN: 41438

American (AMR) AF: 0.764 AC: 11658 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 2437 AN: 3470

East Asian (EAS) AF: 0.905 AC: 4686 AN: 5180

South Asian (SAS) AF: 0.734 AC: 3534 AN: 4814

European-Finnish (FIN) AF: 0.723 AC: 7635 AN: 10558

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46574 AN: 67958

Other (OTH) AF: 0.685 AC: 1445 AN: 2110

Alfa AF: 0.698 Hom.: 155171

Bravo AF: 0.718

Asia WGS AF: 0.804 AC: 2794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.47
DANN	Benign	0.81
PhyloP100		-0.26
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: rs6817264; hg19: chr4-39518110;