rs4788597

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-72009140-C-A
• chr16-72009140-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001361.5(DHODH):​c.21+355C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000991 in 1,009,040 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 29)
  • Exomes 𝑓: 9.9e-7 (0 hom.)
• Consequence: DHODH NM_001361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.500
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Orphanet, G2P

ENSG00000294600 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHODH	NM_001361.5	c.21+355C>A		intron_variant	Intron 1 of 8	ENST00000219240.9	NP_001352.2
DHODH	XM_047433674.1	c.-64+231C>A		intron_variant	Intron 1 of 8		XP_047289630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHODH	ENST00000219240.9	c.21+355C>A		intron_variant	Intron 1 of 8	1	NM_001361.5	ENSP00000219240.4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 9.91e-7 AC: 1 AN: 1009040 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 477004

African (AFR) AF: 0.00 AC: 0 AN: 21938

American (AMR) AF: 0.00 AC: 0 AN: 8922

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10850

East Asian (EAS) AF: 0.00 AC: 0 AN: 14698

South Asian (SAS) AF: 0.00 AC: 0 AN: 36356

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2434

European-Non Finnish (NFE) AF: 0.00000115 AC: 1 AN: 866790

Other (OTH) AF: 0.00 AC: 0 AN: 37852

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.7
DANN	Benign	0.69
PhyloP100		-0.50
PromoterAI		0.0014	Neutral

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

Other links and lift over

dbSNP: rs4788597; hg19: chr16-72043039;