rs148523165

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001361.5(DHODH):c.573G>A(p.Ala191Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,609,634 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0086 ( 7 hom., cov: 32)

Exomes 𝑓: 0.012 ( 137 hom. )

Consequence

DHODH
NM_001361.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.311

Publications

5 publications found

Variant links:

Genes affected

DHODH (HGNC:2867): (dihydroorotate dehydrogenase (quinone)) The protein encoded by this gene catalyzes the fourth enzymatic step, the ubiquinone-mediated oxidation of dihydroorotate to orotate, in de novo pyrimidine biosynthesis. This protein is a mitochondrial protein located on the outer surface of the inner mitochondrial membrane. [provided by RefSeq, Jul 2008]

DHODH Gene-Disease associations (from GenCC):

postaxial acrofacial dysostosis
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P

DHODH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 16-72021179-G-A is Benign according to our data. Variant chr16-72021179-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257968.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.311 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHODH	NM_001361.5 link	c.573G>A	p.Ala191Ala	synonymous_variant	Exon 5 of 9	ENST00000219240.9	NP_001352.2	Q02127
DHODH	XM_047433674.1 link	c.489G>A	p.Ala163Ala	synonymous_variant	Exon 5 of 9		XP_047289630.1
DHODH	XM_005255829.5 link	c.144G>A	p.Ala48Ala	synonymous_variant	Exon 3 of 7		XP_005255886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHODH	ENST00000219240.9 link	c.573G>A	p.Ala191Ala	synonymous_variant	Exon 5 of 9	1	NM_001361.5	ENSP00000219240.4		Q02127

Frequencies

GnomAD3 genomes

AF:

0.00865

AC:

1317

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.00606

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.0101

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0141

Gnomad OTH

AF:

0.0120

GnomAD2 exomes

AF:

0.00801

AC:

1911

AN:

238504

AF XY:

0.00803

show subpopulations

Gnomad AFR exome

AF:

0.00312

Gnomad AMR exome

AF:

0.00420

Gnomad ASJ exome

AF:

0.00754

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00979

Gnomad NFE exome

AF:

0.0128

Gnomad OTH exome

AF:

0.00705

GnomAD4 exome

AF:

0.0117

AC:

17040

AN:

1457304

Hom.:

137

Cov.:

AF XY:

0.0115

AC XY:

8344

AN XY:

724536

show subpopulations

African (AFR)

AF:

0.00189

AC:

AN:

33410

American (AMR)

AF:

0.00428

AC:

189

AN:

44140

Ashkenazi Jewish (ASJ)

AF:

0.00781

AC:

203

AN:

26008

East Asian (EAS)

AF:

0.0000759

AC:

AN:

39506

South Asian (SAS)

AF:

0.00108

AC:

AN:

85318

European-Finnish (FIN)

AF:

0.00951

AC:

503

AN:

52900

Middle Eastern (MID)

AF:

0.00122

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0138

AC:

15301

AN:

1110068

Other (OTH)

AF:

0.0113

AC:

679

AN:

60194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

984

1969

2953

3938

4922

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

568

1136

1704

2272

2840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00864

AC:

1316

AN:

152330

Hom.:

Cov.:

AF XY:

0.00840

AC XY:

626

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00269

AC:

112

AN:

41570

American (AMR)

AF:

0.00490

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00606

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00290

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0101

AC:

107

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0141

AC:

962

AN:

68032

Other (OTH)

AF:

0.0118

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

142

213

284

355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0107

Hom.:

Bravo

AF:

0.00764

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

DHODH: BP4, BP7, BS1, BS2 -

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Miller syndrome

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.4

(source)

DANN

Benign

0.74

PhyloP100

-0.31

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over