rs61747639

Variant names:

• chr16-72014532-C-T
• rs61747639
• NM_001361.5:c.294C>T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001361.5(DHODH):​c.294C>T​(p.Asp98Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00297 in 1,614,168 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (2 hom.)
• Consequence: DHODH NM_001361.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.644

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 16-72014532-C-T is Benign according to our data. Variant chr16-72014532-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 257967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.644 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHODH	NM_001361.5	c.294C>T	p.Asp98Asp	synonymous_variant	Exon 3 of 9	ENST00000219240.9	NP_001352.2
DHODH	XM_047433674.1	c.210C>T	p.Asp70Asp	synonymous_variant	Exon 3 of 9		XP_047289630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHODH	ENST00000219240.9	c.294C>T	p.Asp98Asp	synonymous_variant	Exon 3 of 9	1	NM_001361.5	ENSP00000219240.4

Frequencies

GnomAD3 genomes AF: 0.00218 AC: 331 AN: 152164 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000628

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00321

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00341

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00215 AC: 537 AN: 249580 Hom.: 0 AF XY: 0.00211 AC XY: 286 AN XY: 135410

Gnomad AFR exome AF: 0.000517

Gnomad AMR exome AF: 0.000637

Gnomad ASJ exome AF: 0.00268

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00455

Gnomad NFE exome AF: 0.00325

Gnomad OTH exome AF: 0.00198

GnomAD4 exome AF: 0.00305 AC: 4466 AN: 1461886 Hom.: 2 Cov.: 33 AF XY: 0.00289 AC XY: 2101 AN XY: 727244

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.000715

Gnomad4 ASJ exome AF: 0.00272

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00427

Gnomad4 NFE exome AF: 0.00357

Gnomad4 OTH exome AF: 0.00248

GnomAD4 genome AF: 0.00217 AC: 331 AN: 152282 Hom.: 0 Cov.: 33 AF XY: 0.00227 AC XY: 169 AN XY: 74458

Gnomad4 AFR AF: 0.000626

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00321

Gnomad4 NFE AF: 0.00341

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00283 Hom.: 0

Bravo AF: 0.00183

EpiCase AF: 0.00393

EpiControl AF: 0.00279

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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: Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not provided Benign:1

Jan 13, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	9.1
DANN	Benign	0.64

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: rs61747639; hg19: chr16-72048431;