rs11666105

chr19-48942560-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014475.4(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 NM_014475.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.93

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 -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	UniProt
DHDH	NM_014475.4	c.740T>C	p.Val247Ala	missense_variant	5/7	ENST00000221403.7
DHDH	XM_017026598.2	c.491T>C	p.Val164Ala	missense_variant	5/7
DHDH	XM_005258748.5	c.404T>C	p.Val135Ala	missense_variant	4/6
DHDH	XM_047438617.1	c.620-1797T>C		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51484 AN: 151942 Hom.: 11780 Cov.: 32

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

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.: 32 AF XY: 0.214 AC XY: 155274 AN XY: 726470

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.: 32 AF XY: 0.346 AC XY: 25695 AN XY: 74340

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	T
BayesDel_noAF	Benign	-0.74
Cadd	Benign	17
Dann	Benign	0.65
DEOGEN2	Benign	0.20	T;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.19	T;T
MetaRNN	Benign	0.000013	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.70	N;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.40	T
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	T
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

Other links and lift over

dbSNP: rs11666105; hg19: chr19-49445817; COSMIC: COSV55481779;