16-72009140-C-T

Variant names:

• chr16-72009140-C-T
• rs4788597
• NM_001361.5:c.21+355C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001361.5(DHODH):​c.21+355C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 1,159,170 control chromosomes in the GnomAD database, including 82,921 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 0.43 (14588 hom., cov: 29)
  • Exomes 𝑓: 0.36 (68333 hom.)
• Consequence: DHODH NM_001361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.500
• Publications: 13 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, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000294600 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001361.5. 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.21+355C>T		intron	N/A	NP_001352.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHODH	ENST00000219240.9	TSL:1 MANE Select	c.21+355C>T		intron	N/A	ENSP00000219240.4	Q02127
	DHODH	ENST00000576145.1	TSL:5	c.-71C>T		5_prime_UTR	Exon 1 of 4	ENSP00000464333.1	J3QRQ3
	DHODH	ENST00000894311.1		c.21+355C>T		intron	N/A	ENSP00000564370.1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64667 AN: 151664 Hom.: 14572 Cov.: 29

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.385

GnomAD4 exome AF: 0.363 AC: 365791 AN: 1007388 Hom.: 68333 Cov.: 30 AF XY: 0.361 AC XY: 171717 AN XY: 476138

African (AFR) AF: 0.503 AC: 11017 AN: 21886

American (AMR) AF: 0.526 AC: 4657 AN: 8854

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 2607 AN: 10816

East Asian (EAS) AF: 0.675 AC: 9881 AN: 14628

South Asian (SAS) AF: 0.270 AC: 9768 AN: 36192

European-Finnish (FIN) AF: 0.317 AC: 2903 AN: 9144

Middle Eastern (MID) AF: 0.238 AC: 576 AN: 2424

European-Non Finnish (NFE) AF: 0.359 AC: 310555 AN: 865672

Other (OTH) AF: 0.366 AC: 13827 AN: 37772

GnomAD4 genome AF: 0.426 AC: 64734 AN: 151782 Hom.: 14588 Cov.: 29 AF XY: 0.429 AC XY: 31824 AN XY: 74170

African (AFR) AF: 0.517 AC: 21394 AN: 41366

American (AMR) AF: 0.525 AC: 8010 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 896 AN: 3470

East Asian (EAS) AF: 0.731 AC: 3749 AN: 5132

South Asian (SAS) AF: 0.302 AC: 1451 AN: 4808

European-Finnish (FIN) AF: 0.344 AC: 3626 AN: 10538

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24255 AN: 67898

Other (OTH) AF: 0.387 AC: 815 AN: 2106

Alfa AF: 0.378 Hom.: 35781

Bravo AF: 0.449

Asia WGS AF: 0.512 AC: 1777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.2
DANN	Benign	0.74
PhyloP100		-0.50
PromoterAI		0.0096	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4788597;

hg19: chr16-72043039;