NM_014475.4:c.881_882delAG

Variant names:

• chr19-48944491-GGA-G
• rs3835153
• NM_014475.4:c.881_882delAG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_014475.4(DHDH):​c.881_882delAG​(p.Glu294ValfsTer18) 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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014475.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHDH	NM_014475.4	MANE Select	c.881_882delAG	p.Glu294ValfsTer18	frameshift	Exon 6 of 7	NP_055290.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHDH	ENST00000221403.7	TSL:1 MANE Select	c.881_882delAG	p.Glu294ValfsTer18	frameshift	Exon 6 of 7	ENSP00000221403.2
	DHDH	ENST00000523250.5	TSL:5	c.464_465delAG	p.Glu155ValfsTer18	frameshift	Exon 4 of 5	ENSP00000428935.1
	DHDH	ENST00000520557.1	TSL:5	n.*142_*143delAG		non_coding_transcript_exon	Exon 4 of 5	ENSP00000430360.1

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

GnomAD2 exomes AF: 0.0769 AC: 19128 AN: 248690 AF XY: 0.0767

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 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

African (AFR) AF: 0.0110 AC: 369 AN: 33400

American (AMR) AF: 0.0771 AC: 3428 AN: 44444

Ashkenazi Jewish (ASJ) AF: 0.0163 AC: 423 AN: 25904

East Asian (EAS) AF: 0.0463 AC: 1831 AN: 39556

South Asian (SAS) AF: 0.0558 AC: 4792 AN: 85846

European-Finnish (FIN) AF: 0.201 AC: 10739 AN: 53302

Middle Eastern (MID) AF: 0.0271 AC: 156 AN: 5758

European-Non Finnish (NFE) AF: 0.0773 AC: 85599 AN: 1108052

Other (OTH) AF: 0.0666 AC: 4006 AN: 60116

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

African (AFR) AF: 0.0128 AC: 532 AN: 41538

American (AMR) AF: 0.0721 AC: 1101 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 57 AN: 3470

East Asian (EAS) AF: 0.0468 AC: 243 AN: 5188

South Asian (SAS) AF: 0.0630 AC: 304 AN: 4826

European-Finnish (FIN) AF: 0.217 AC: 2300 AN: 10584

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0787 AC: 5354 AN: 67996

Other (OTH) AF: 0.0568 AC: 120 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.7
Mutation Taster		=117/83	polymorphism (auto)

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: rs3835153; hg19: chr19-49447748; COSMIC: COSV55481510;