Variant chr19-48939676-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_014475.4(DHDH):c.594T>C(p.Ser198=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,603,172 control chromosomes in the GnomAD database, including 53,048 homozygotes. 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: 𝑓 0.34 ( 11900 hom., cov: 31)

Exomes 𝑓: 0.21 ( 41148 hom. )

Consequence

DHDH
NM_014475.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.63

Variant links:

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]

DHDH links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP7

Synonymous conserved (PhyloP=-2.63 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DHDH	NM_014475.4 linkuse as main transcript	c.594T>C	p.Ser198=	synonymous_variant	4/7	ENST00000221403.7	NP_055290.1
DHDH	XM_017026598.2 linkuse as main transcript	c.345T>C	p.Ser115=	synonymous_variant	4/7		XP_016882087.1
DHDH	XM_047438617.1 linkuse as main transcript	c.594T>C	p.Ser198=	synonymous_variant	4/5		XP_047294573.1
DHDH	XM_005258748.5 linkuse as main transcript	c.258T>C	p.Ser86=	synonymous_variant	3/6		XP_005258805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
DHDH	ENST00000221403.7 linkuse as main transcript	c.594T>C	p.Ser198=	synonymous_variant	4/7	1	NM_014475.4	ENSP00000221403	P1
DHDH	ENST00000522614.5 linkuse as main transcript	c.594T>C	p.Ser198=	synonymous_variant	4/5	5		ENSP00000428672
DHDH	ENST00000523250.5 linkuse as main transcript	c.203-2764T>C		intron_variant		5		ENSP00000428935
DHDH	ENST00000520557.1 linkuse as main transcript	c.394T>C	p.Cys132Arg	missense_variant, NMD_transcript_variant	3/5	5		ENSP00000430360

Frequencies

GnomAD3 genomes

AF:

0.340

AC:

51593

AN:

151890

Hom.:

11852

Cov.:

show subpopulations

Gnomad AFR

AF:

0.636

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.560

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.328

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.171

Gnomad OTH

AF:

0.301

GnomAD3 exomes

AF:

0.281

AC:

70016

AN:

249440

Hom.:

12685

AF XY:

0.272

AC XY:

36707

AN XY:

134906

show subpopulations

Gnomad AFR exome

AF:

0.646

Gnomad AMR exome

AF:

0.273

Gnomad ASJ exome

AF:

0.187

Gnomad EAS exome

AF:

0.556

Gnomad SAS exome

AF:

0.349

Gnomad FIN exome

AF:

0.314

Gnomad NFE exome

AF:

0.172

Gnomad OTH exome

AF:

0.235

GnomAD4 exome

AF:

0.212

AC:

307976

AN:

1451164

Hom.:

41148

Cov.:

AF XY:

0.214

AC XY:

153967

AN XY:

719718

show subpopulations

Gnomad4 AFR exome

AF:

0.653

Gnomad4 AMR exome

AF:

0.274

Gnomad4 ASJ exome

AF:

0.186

Gnomad4 EAS exome

AF:

0.551

Gnomad4 SAS exome

AF:

0.348

Gnomad4 FIN exome

AF:

0.306

Gnomad4 NFE exome

AF:

0.168

Gnomad4 OTH exome

AF:

0.247

GnomAD4 genome

AF:

0.340

AC:

51704

AN:

152008

Hom.:

11900

Cov.:

AF XY:

0.346

AC XY:

25728

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.637

Gnomad4 AMR

AF:

0.265

Gnomad4 ASJ

AF:

0.195

Gnomad4 EAS

AF:

0.561

Gnomad4 SAS

AF:

0.371

Gnomad4 FIN

AF:

0.328

Gnomad4 NFE

AF:

0.171

Gnomad4 OTH

AF:

0.305

Alfa

AF:

0.198

Hom.:

5186

Bravo

AF:

0.348

Asia WGS

AF:

0.478

AC:

1660

AN:

3478

EpiCase

AF:

0.171

EpiControl

AF:

0.164

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.045

DANN

Benign

0.25

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over