rs7669821

Variant names:

• chr4-39520603-C-T
• rs7669821
• NM_003359.4:c.162+748G>A

Variant summary

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

The NM_003359.4(UGDH):​c.162+748G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,690 control chromosomes in the GnomAD database, including 20,118 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 0.49 (20118 hom., cov: 32)
• Consequence: UGDH NM_003359.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGDH	NM_003359.4	c.162+748G>A		intron_variant	Intron 2 of 11	ENST00000316423.11	NP_003350.1
UGDH	NM_001184700.2	c.162+748G>A		intron_variant	Intron 2 of 10		NP_001171629.1
UGDH	NM_001184701.2	c.-129-6419G>A		intron_variant	Intron 1 of 10		NP_001171630.1
UGDH	XM_005262667.4	c.201+748G>A		intron_variant	Intron 2 of 11		XP_005262724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGDH	ENST00000316423.11	c.162+748G>A		intron_variant	Intron 2 of 11	1	NM_003359.4	ENSP00000319501.6

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73657 AN: 151570 Hom.: 20115 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.486 AC: 73667 AN: 151690 Hom.: 20118 Cov.: 32 AF XY: 0.494 AC XY: 36617 AN XY: 74164

African (AFR) AF: 0.224 AC: 9281 AN: 41378

American (AMR) AF: 0.587 AC: 8966 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.536 AC: 1857 AN: 3466

East Asian (EAS) AF: 0.502 AC: 2594 AN: 5170

South Asian (SAS) AF: 0.572 AC: 2757 AN: 4822

European-Finnish (FIN) AF: 0.635 AC: 6580 AN: 10358

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.588 AC: 39955 AN: 67920

Other (OTH) AF: 0.459 AC: 967 AN: 2108

Alfa AF: 0.562 Hom.: 26864

Bravo AF: 0.468

Asia WGS AF: 0.464 AC: 1606 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	13
DANN	Benign	0.69
PhyloP100		-0.025
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: rs7669821; hg19: chr4-39522223;