16-72008736-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000572887.5(DHODH):c.-29A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0892 in 1,551,414 control chromosomes in the GnomAD database, including 7,211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.063 (438 hom., cov: 35)
  • Exomes 𝑓: 0.092 (6773 hom.)
• Consequence: DHODH ENST00000572887.5 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.79

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 16-72008736-A-G is Benign according to our data. Variant chr16-72008736-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 369126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHODH	NM_001361.5			upstream_gene_variant		ENST00000219240.9
DHODH	XM_047433674.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHODH	ENST00000572887.5	c.-29A>G		5_prime_UTR_variant	1/9	5		A1
DHODH	ENST00000219240.9			upstream_gene_variant		1	NM_001361.5	P3
DHODH	ENST00000574309.5			upstream_gene_variant		5
DHODH	ENST00000571288.6			upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0633 AC: 9633 AN: 152224 Hom.: 439 Cov.: 35

Gnomad AFR AF: 0.0188

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0625

Gnomad ASJ AF: 0.0792

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.0576

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0991

Gnomad OTH AF: 0.0636

GnomAD3 exomes AF: 0.0613 AC: 9464 AN: 154514 Hom.: 417 AF XY: 0.0609 AC XY: 4979 AN XY: 81804

Gnomad AFR exome AF: 0.0172

Gnomad AMR exome AF: 0.0454

Gnomad ASJ exome AF: 0.0808

Gnomad EAS exome AF: 0.0000917

Gnomad SAS exome AF: 0.0152

Gnomad FIN exome AF: 0.0553

Gnomad NFE exome AF: 0.100

Gnomad OTH exome AF: 0.0685

GnomAD4 exome AF: 0.0920 AC: 128728 AN: 1399072 Hom.: 6773 Cov.: 31 AF XY: 0.0901 AC XY: 62152 AN XY: 690048

Gnomad4 AFR exome AF: 0.0144

Gnomad4 AMR exome AF: 0.0474

Gnomad4 ASJ exome AF: 0.0818

Gnomad4 EAS exome AF: 0.0000839

Gnomad4 SAS exome AF: 0.0166

Gnomad4 FIN exome AF: 0.0581

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.0817

GnomAD4 genome AF: 0.0632 AC: 9628 AN: 152342 Hom.: 438 Cov.: 35 AF XY: 0.0588 AC XY: 4382 AN XY: 74492

Gnomad4 AFR AF: 0.0187

Gnomad4 AMR AF: 0.0625

Gnomad4 ASJ AF: 0.0792

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0151

Gnomad4 FIN AF: 0.0576

Gnomad4 NFE AF: 0.0991

Gnomad4 OTH AF: 0.0634

Alfa AF: 0.0667 Hom.: 168

Bravo AF: 0.0633

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Miller syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.0
Dann	Benign	0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34270657; hg19: chr16-72042635;