chr16-72008926-T-G

Position:

• chr16-72008926-T-G

Variant summary

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

The NM_001361.5(DHODH):​c.21+141T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 1,529,302 control chromosomes in the GnomAD database, including 462,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (51859 hom., cov: 31)
  • Exomes 𝑓: 0.77 (410592 hom.)
• Consequence: DHODH NM_001361.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.723

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=-0.89).
• BP6: Variant 16-72008926-T-G is Benign according to our data. Variant chr16-72008926-T-G is described in ClinVar as [Benign]. Clinvar id is 1229459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHODH	NM_001361.5	c.21+141T>G		intron_variant		ENST00000219240.9
DHODH	XM_047433674.1	c.-64+17T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHODH	ENST00000219240.9	c.21+141T>G		intron_variant		1	NM_001361.5	P3

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124747 AN: 151942 Hom.: 51799 Cov.: 31

Gnomad AFR AF: 0.932

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.962

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.731

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.799

GnomAD4 exome AF: 0.770 AC: 1060869 AN: 1377242 Hom.: 410592 Cov.: 51 AF XY: 0.770 AC XY: 521154 AN XY: 677030

Gnomad4 AFR exome AF: 0.934

Gnomad4 AMR exome AF: 0.884

Gnomad4 ASJ exome AF: 0.682

Gnomad4 EAS exome AF: 0.959

Gnomad4 SAS exome AF: 0.787

Gnomad4 FIN exome AF: 0.744

Gnomad4 NFE exome AF: 0.757

Gnomad4 OTH exome AF: 0.778

GnomAD4 genome AF: 0.821 AC: 124868 AN: 152060 Hom.: 51859 Cov.: 31 AF XY: 0.820 AC XY: 60968 AN XY: 74312

Gnomad4 AFR AF: 0.932

Gnomad4 AMR AF: 0.853

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.962

Gnomad4 SAS AF: 0.788

Gnomad4 FIN AF: 0.731

Gnomad4 NFE AF: 0.760

Gnomad4 OTH AF: 0.801

Alfa AF: 0.798 Hom.: 13500

Bravo AF: 0.836

Asia WGS AF: 0.885 AC: 3075 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs3213423; hg19: chr16-72042825;