dbSNP rs7667766: UGDH:c.1374+1190G>T (chr4-39502685-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.396

Publications

12 publications found

Variant links:

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

UGDH links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003359.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
UGDH	NM_003359.4	MANE Select	c.1374+1190G>T	intron	N/A	NP_003350.1
UGDH	NM_001184700.2		c.1173+1190G>T	intron	N/A	NP_001171629.1
UGDH	NM_001184701.2		c.1083+1190G>T	intron	N/A	NP_001171630.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
UGDH	ENST00000316423.11	TSL:1 MANE Select	c.1374+1190G>T	intron	N/A	ENSP00000319501.6
UGDH	ENST00000907836.1		c.1482+1190G>T	intron	N/A	ENSP00000577895.1
UGDH	ENST00000907837.1		c.1464+1190G>T	intron	N/A	ENSP00000577896.1

Frequencies

GnomAD3 genomes

AF:

0.638

AC:

96940

AN:

152026

Hom.:

31281

Cov.:

show subpopulations

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.:

AF XY:

0.644

AC XY:

47918

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.585

AC:

24276

AN:

41496

American (AMR)

AF:

0.700

AC:

10695

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.646

AC:

2241

AN:

3468

East Asian (EAS)

AF:

0.861

AC:

4460

AN:

5182

South Asian (SAS)

AF:

0.591

AC:

2849

AN:

4818

European-Finnish (FIN)

AF:

0.704

AC:

7451

AN:

10580

Middle Eastern (MID)

AF:

0.524

AC:

154

AN:

294

European-Non Finnish (NFE)

AF:

0.632

AC:

42995

AN:

67996

Other (OTH)

AF:

0.599

AC:

1267

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1796

3592

5387

7183

8979

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

786

1572

2358

3144

3930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.624

Hom.:

48495

Bravo

AF:

0.635

Asia WGS

AF:

0.666

AC:

2315

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.3

(source)

DANN

Benign

0.78

PhyloP100

0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over