rs4788597

Positions:

• chr16-72009140-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHODH	NM_001361.5	c.21+355C>T		intron_variant		ENST00000219240.9	NP_001352.2
DHODH	XM_047433674.1	c.-64+231C>T		intron_variant			XP_047289630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHODH	ENST00000219240.9	c.21+355C>T		intron_variant		1	NM_001361.5	ENSP00000219240	P3

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

Gnomad4 AFR exome AF: 0.503

Gnomad4 AMR exome AF: 0.526

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.675

Gnomad4 SAS exome AF: 0.270

Gnomad4 FIN exome AF: 0.317

Gnomad4 NFE exome AF: 0.359

Gnomad4 OTH exome AF: 0.366

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

Gnomad4 AFR AF: 0.517

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.731

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.387

Alfa AF: 0.365 Hom.: 21471

Bravo AF: 0.449

Asia WGS AF: 0.512 AC: 1777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.2
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs4788597; hg19: chr16-72043039;