chr19-48942560-T-C

Variant names:

• chr19-48942560-T-C
• rs11666105
• NM_014475.4:c.740T>C

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict 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 (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
• Publications: 25 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 -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.

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.740T>C	p.Val247Ala	missense	Exon 5 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.740T>C	p.Val247Ala	missense	Exon 5 of 7	ENSP00000221403.2
	DHDH	ENST00000523250.5	TSL:5	c.323T>C	p.Val108Ala	missense	Exon 3 of 5	ENSP00000428935.1
	DHDH	ENST00000522614.5	TSL:5	c.620-2264T>C		intron	N/A	ENSP00000428672.1

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

GnomAD2 exomes AF: 0.280 AC: 70080 AN: 249900 AF XY: 0.272

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 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

African (AFR) AF: 0.650 AC: 21753 AN: 33450

American (AMR) AF: 0.274 AC: 12208 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 4852 AN: 26072

East Asian (EAS) AF: 0.551 AC: 21865 AN: 39690

South Asian (SAS) AF: 0.348 AC: 29967 AN: 86136

European-Finnish (FIN) AF: 0.305 AC: 16238 AN: 53160

Middle Eastern (MID) AF: 0.207 AC: 1190 AN: 5758

European-Non Finnish (NFE) AF: 0.168 AC: 186751 AN: 1111100

Other (OTH) AF: 0.247 AC: 14876 AN: 60308

GnomAD4 genome AF: 0.339 AC: 51592 AN: 152060 Hom.: 11827 Cov.: 32 AF XY: 0.346 AC XY: 25695 AN XY: 74340

African (AFR) AF: 0.634 AC: 26266 AN: 41450

American (AMR) AF: 0.264 AC: 4031 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 677 AN: 3472

East Asian (EAS) AF: 0.562 AC: 2907 AN: 5170

South Asian (SAS) AF: 0.372 AC: 1797 AN: 4828

European-Finnish (FIN) AF: 0.328 AC: 3472 AN: 10584

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11600 AN: 67978

Other (OTH) AF: 0.305 AC: 646 AN: 2116

Alfa AF: 0.223 Hom.: 24592

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 v4.9

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
MetaRNN	Benign	0.000013	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.70	N
PhyloP100		2.9
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.069
Sift	Benign	0.35	T
Sift4G	Benign	0.17	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
Mutation Taster		=99/1	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: rs11666105; hg19: chr19-49445817; COSMIC: COSV55481779;