Variant 19-48942560-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000221403.7(DHDH):c.740T>C(p.Val247Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,612,318 control chromosomes in the GnomAD database, including 53,160 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.34 ( 11827 hom., cov: 32)

Exomes 𝑓: 0.21 ( 41333 hom. )

Consequence

DHDH
ENST00000221403.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.93

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2545386E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 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.740T>C	p.Val247Ala	missense_variant	5/7	ENST00000221403.7	NP_055290.1
DHDH	XM_017026598.2 linkuse as main transcript	c.491T>C	p.Val164Ala	missense_variant	5/7		XP_016882087.1
DHDH	XM_005258748.5 linkuse as main transcript	c.404T>C	p.Val135Ala	missense_variant	4/6		XP_005258805.1
DHDH	XM_047438617.1 linkuse as main transcript	c.620-1797T>C		intron_variant			XP_047294573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
DHDH	ENST00000221403.7 linkuse as main transcript	c.740T>C	p.Val247Ala	missense_variant	5/7	1	NM_014475.4	ENSP00000221403	P1
DHDH	ENST00000523250.5 linkuse as main transcript	c.323T>C	p.Val108Ala	missense_variant	3/5	5		ENSP00000428935
DHDH	ENST00000522614.5 linkuse as main transcript	c.620-2264T>C		intron_variant		5		ENSP00000428672
DHDH	ENST00000520557.1 linkuse as main transcript	c.*6-1797T>C		intron_variant, NMD_transcript_variant		5		ENSP00000430360

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

51484

AN:

151942

Hom.:

11780

Cov.:

show subpopulations

Gnomad AFR

AF:

0.633

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.264

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.561

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.328

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.171

Gnomad OTH

AF:

0.302

GnomAD3 exomes

AF:

0.280

AC:

70080

AN:

249900

Hom.:

12667

AF XY:

0.272

AC XY:

36765

AN XY:

135170

show subpopulations

Gnomad AFR exome

AF:

0.643

Gnomad AMR exome

AF:

0.272

Gnomad ASJ exome

AF:

0.186

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:

309700

AN:

1460258

Hom.:

41333

Cov.:

AF XY:

0.214

AC XY:

155274

AN XY:

726470

show subpopulations

Gnomad4 AFR exome

AF:

0.650

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:

0.305

Gnomad4 NFE exome

AF:

0.168

Gnomad4 OTH exome

AF:

0.247

GnomAD4 genome

AF:

0.339

AC:

51592

AN:

152060

Hom.:

11827

Cov.:

AF XY:

0.346

AC XY:

25695

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.634

Gnomad4 AMR

AF:

0.264

Gnomad4 ASJ

AF:

0.195

Gnomad4 EAS

AF:

0.562

Gnomad4 SAS

AF:

0.372

Gnomad4 FIN

AF:

0.328

Gnomad4 NFE

AF:

0.171

Gnomad4 OTH

AF:

0.305

Alfa

AF:

0.204

Hom.:

9936

Bravo

AF:

0.346

TwinsUK

AF:

0.160

AC:

593

ALSPAC

AF:

0.165

AC:

637

ESP6500AA

AF:

0.629

AC:

2770

ESP6500EA

AF:

0.173

AC:

1489

ExAC

AF:

0.285

AC:

34631

Asia WGS

AF:

0.479

AC:

1663

AN:

3478

EpiCase

AF:

0.171

EpiControl

AF:

0.163

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.65

DEOGEN2

Benign

0.20

T;.

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.19

T;T

MetaRNN

Benign

0.000013

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.70

N;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.6

D;N

REVEL

Benign

0.069

Sift

Benign

0.35

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.0

B;.

Vest4

0.099

MPC

0.15

ClinPred

0.018

GERP RS

2.5

Varity_R

0.087

gMVP

0.57

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