Variant chr14-23959985-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_021004.4(DHRS4):c.390T>C(p.Thr130=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0418 in 1,595,660 control chromosomes in the GnomAD database, including 11,243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.16 ( 5470 hom., cov: 28)

Exomes 𝑓: 0.030 ( 5773 hom. )

Consequence

DHRS4
NM_021004.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.52

Variant links:

Genes affected

DHRS4 (HGNC:16985): (dehydrogenase/reductase 4) Enables identical protein binding activity; oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor; and oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor. Involved in several processes, including cellular ketone metabolic process; positive regulation of reactive oxygen species metabolic process; and steroid metabolic process. Located in nucleus and peroxisomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

DHRS4 links:

DHRS4-AS1 (HGNC:23175): (DHRS4 antisense RNA 1)

DHRS4-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 14-23959985-T-C is Benign according to our data. Variant chr14-23959985-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 768639.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.52 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHRS4	NM_021004.4 linkuse as main transcript	c.390T>C	p.Thr130=	synonymous_variant	3/8	ENST00000313250.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHRS4	ENST00000313250.10 linkuse as main transcript	c.390T>C	p.Thr130=	synonymous_variant	3/8	1	NM_021004.4	P1	Q9BTZ2-1
DHRS4-AS1	ENST00000656462.1 linkuse as main transcript	n.213-18827A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.162

AC:

23253

AN:

143522

Hom.:

5443

Cov.:

show subpopulations

Gnomad AFR

AF:

0.528

Gnomad AMI

AF:

0.0216

Gnomad AMR

AF:

0.0698

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.00283

Gnomad SAS

AF:

0.0106

Gnomad FIN

AF:

0.0664

Gnomad MID

AF:

0.0385

Gnomad NFE

AF:

0.0202

Gnomad OTH

AF:

0.133

GnomAD3 exomes

AF:

0.0543

AC:

13580

AN:

249980

Hom.:

2523

AF XY:

0.0444

AC XY:

6004

AN XY:

135258

show subpopulations

Gnomad AFR exome

AF:

0.530

Gnomad AMR exome

AF:

0.0365

Gnomad ASJ exome

AF:

0.0184

Gnomad EAS exome

AF:

0.00359

Gnomad SAS exome

AF:

0.00782

Gnomad FIN exome

AF:

0.0517

Gnomad NFE exome

AF:

0.0190

Gnomad OTH exome

AF:

0.0375

GnomAD4 exome

AF:

0.0298

AC:

43339

AN:

1452036

Hom.:

5773

Cov.:

AF XY:

0.0277

AC XY:

20036

AN XY:

722750

show subpopulations

Gnomad4 AFR exome

AF:

0.543

Gnomad4 AMR exome

AF:

0.0398

Gnomad4 ASJ exome

AF:

0.0186

Gnomad4 EAS exome

AF:

0.00404

Gnomad4 SAS exome

AF:

0.00911

Gnomad4 FIN exome

AF:

0.0517

Gnomad4 NFE exome

AF:

0.0151

Gnomad4 OTH exome

AF:

0.0473

GnomAD4 genome

AF:

0.162

AC:

23324

AN:

143624

Hom.:

5470

Cov.:

AF XY:

0.160

AC XY:

11071

AN XY:

69300

show subpopulations

Gnomad4 AFR

AF:

0.529

Gnomad4 AMR

AF:

0.0698

Gnomad4 ASJ

AF:

0.0170

Gnomad4 EAS

AF:

0.00283

Gnomad4 SAS

AF:

0.0104

Gnomad4 FIN

AF:

0.0664

Gnomad4 NFE

AF:

0.0202

Gnomad4 OTH

AF:

0.131

Alfa

AF:

0.0529

Hom.:

448

Bravo

AF:

0.185

EpiCase

AF:

0.0181

EpiControl

AF:

0.0180

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.037

DANN

Benign

0.51

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over