ENST00000572887.5:c.-29A>G

Variant names:

• chr16-72008736-A-G
• rs34270657
• ENST00000572887.5:c.-29A>G

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: -1.79
• Publications: 5 publications found

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: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000294600 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000572887.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHODH	NM_001361.5	MANE Select	c.-29A>G		upstream_gene	N/A	NP_001352.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHODH	ENST00000572887.5	TSL:5	c.-29A>G		5_prime_UTR	Exon 1 of 9	ENSP00000461848.1	I3NI32
	ENSG00000294600	ENST00000724668.1		n.292-2744T>C		intron	N/A
	ENSG00000294600	ENST00000724669.1		n.223-1941T>C		intron	N/A

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

GnomAD2 exomes AF: 0.0613 AC: 9464 AN: 154514 AF XY: 0.0609

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 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

African (AFR) AF: 0.0144 AC: 456 AN: 31584

American (AMR) AF: 0.0474 AC: 1691 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.0818 AC: 2059 AN: 25176

East Asian (EAS) AF: 0.0000839 AC: 3 AN: 35736

South Asian (SAS) AF: 0.0166 AC: 1316 AN: 79224

European-Finnish (FIN) AF: 0.0581 AC: 2864 AN: 49268

Middle Eastern (MID) AF: 0.0449 AC: 250 AN: 5562

European-Non Finnish (NFE) AF: 0.107 AC: 115350 AN: 1078838

Other (OTH) AF: 0.0817 AC: 4739 AN: 57984

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

African (AFR) AF: 0.0187 AC: 779 AN: 41598

American (AMR) AF: 0.0625 AC: 957 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0792 AC: 275 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.0151 AC: 73 AN: 4830

European-Finnish (FIN) AF: 0.0576 AC: 611 AN: 10612

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0991 AC: 6739 AN: 68014

Other (OTH) AF: 0.0634 AC: 134 AN: 2114

Alfa AF: 0.0686 Hom.: 202

Bravo AF: 0.0633

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Miller syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.69
PhyloP100		-1.8
PromoterAI		0.040	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs34270657; hg19: chr16-72042635;