rs3835153

Positions:

• chr19-48944491-GGA-G
• chr19-48944491-GGA-GGAGA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_014475.4(DHDH):​c.881_882delAG​(p.Glu294fs) variant causes a frameshift change. The variant allele was found at a frequency of 0.0755 in 1,608,572 control chromosomes in the GnomAD database, including 5,474 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.066 (526 hom., cov: 31)
  • Exomes 𝑓: 0.076 (4948 hom.)
• Consequence: DHDH NM_014475.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.69

Genes affected

DHDH (HGNC:17887): (dihydrodiol dehydrogenase) This gene encodes an enzyme that belongs to the family of dihydrodiol dehydrogenases, which exist in multiple forms in mammalian tissues and are involved in the metabolism of xenobiotics and sugars. These enzymes catalyze the NADP1-linked oxidation of transdihydrodiols of aromatic hydrocarbons to corresponding catechols. This enzyme is a dimeric dihydrodiol dehydrogenase, and it differs from monomeric dihydrodiol dehydrogenases in its high substrate specificity for trans-dihydrodiols of aromatic hydrocarbons in the oxidative direction. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.077 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHDH	NM_014475.4	c.881_882delAG	p.Glu294fs	frameshift_variant	6/7	ENST00000221403.7	NP_055290.1
DHDH	XM_017026598.2	c.632_633delAG	p.Glu211fs	frameshift_variant	6/7		XP_016882087.1
DHDH	XM_005258748.5	c.545_546delAG	p.Glu182fs	frameshift_variant	5/6		XP_005258805.1
DHDH	XM_047438617.1	c.*84_*85delAG		3_prime_UTR_variant	5/5		XP_047294573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHDH	ENST00000221403.7	c.881_882delAG	p.Glu294fs	frameshift_variant	6/7	1	NM_014475.4	ENSP00000221403.2

Frequencies

GnomAD3 genomes AF: 0.0662 AC: 10062 AN: 152076 Hom.: 524 Cov.: 31

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0719

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.0469

Gnomad SAS AF: 0.0629

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0787

Gnomad OTH AF: 0.0578

GnomAD3 exomes AF: 0.0769 AC: 19128 AN: 248690 Hom.: 1018 AF XY: 0.0767 AC XY: 10305 AN XY: 134334

Gnomad AFR exome AF: 0.0115

Gnomad AMR exome AF: 0.0748

Gnomad ASJ exome AF: 0.0191

Gnomad EAS exome AF: 0.0474

Gnomad SAS exome AF: 0.0582

Gnomad FIN exome AF: 0.208

Gnomad NFE exome AF: 0.0774

Gnomad OTH exome AF: 0.0691

GnomAD4 exome AF: 0.0765 AC: 111343 AN: 1456378 Hom.: 4948 AF XY: 0.0756 AC XY: 54677 AN XY: 723556

Gnomad4 AFR exome AF: 0.0110

Gnomad4 AMR exome AF: 0.0771

Gnomad4 ASJ exome AF: 0.0163

Gnomad4 EAS exome AF: 0.0463

Gnomad4 SAS exome AF: 0.0558

Gnomad4 FIN exome AF: 0.201

Gnomad4 NFE exome AF: 0.0773

Gnomad4 OTH exome AF: 0.0666

GnomAD4 genome AF: 0.0661 AC: 10063 AN: 152194 Hom.: 526 Cov.: 31 AF XY: 0.0726 AC XY: 5399 AN XY: 74400

Gnomad4 AFR AF: 0.0128

Gnomad4 AMR AF: 0.0721

Gnomad4 ASJ AF: 0.0164

Gnomad4 EAS AF: 0.0468

Gnomad4 SAS AF: 0.0630

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.0787

Gnomad4 OTH AF: 0.0568

Alfa AF: 0.0196 Hom.: 178

Bravo AF: 0.0525

Asia WGS AF: 0.0590 AC: 204 AN: 3478

EpiCase AF: 0.0693

EpiControl AF: 0.0661

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs3835153; hg19: chr19-49447748;