chr16-72014532-C-T

Variant names:

• chr16-72014532-C-T
• rs61747639
• NM_001361.5:c.294C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001361.5(DHODH):​c.294C>T​(p.Asp98Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00297 in 1,614,168 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (2 hom.)
• Consequence: DHODH NM_001361.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.644
• Publications: 1 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: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 16-72014532-C-T is Benign according to our data. Variant chr16-72014532-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.644 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.294C>T	p.Asp98Asp	synonymous	Exon 3 of 9	NP_001352.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHODH	ENST00000219240.9	TSL:1 MANE Select	c.294C>T	p.Asp98Asp	synonymous	Exon 3 of 9	ENSP00000219240.4
	DHODH	ENST00000894311.1		c.294C>T	p.Asp98Asp	synonymous	Exon 3 of 11	ENSP00000564370.1
	DHODH	ENST00000894313.1		c.291C>T	p.Asp97Asp	synonymous	Exon 3 of 9	ENSP00000564372.1

Frequencies

GnomAD3 genomes AF: 0.00218 AC: 331 AN: 152164 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000628

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00321

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00341

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00215 AC: 537 AN: 249580 AF XY: 0.00211

Gnomad AFR exome AF: 0.000517

Gnomad AMR exome AF: 0.000637

Gnomad ASJ exome AF: 0.00268

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00455

Gnomad NFE exome AF: 0.00325

Gnomad OTH exome AF: 0.00198

GnomAD4 exome AF: 0.00305 AC: 4466 AN: 1461886 Hom.: 2 Cov.: 33 AF XY: 0.00289 AC XY: 2101 AN XY: 727244

African (AFR) AF: 0.000478 AC: 16 AN: 33480

American (AMR) AF: 0.000715 AC: 32 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00272 AC: 71 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86256

European-Finnish (FIN) AF: 0.00427 AC: 228 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00357 AC: 3966 AN: 1112008

Other (OTH) AF: 0.00248 AC: 150 AN: 60396

GnomAD4 genome AF: 0.00217 AC: 331 AN: 152282 Hom.: 0 Cov.: 33 AF XY: 0.00227 AC XY: 169 AN XY: 74458

African (AFR) AF: 0.000626 AC: 26 AN: 41556

American (AMR) AF: 0.00124 AC: 19 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00321 AC: 34 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00341 AC: 232 AN: 68040

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00279 Hom.: 0

Bravo AF: 0.00183

EpiCase AF: 0.00393

EpiControl AF: 0.00279

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	9.1
DANN	Benign	0.64
PhyloP100		0.64
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs61747639; hg19: chr16-72048431;