Genetic Variant DHRS4L2:p.Arg14Gly (chr14-23988987-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_198083.4(DHRS4L2):c.40C>G(p.Arg14Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000054 in 1,611,410 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R14W) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000032 ( 2 hom. )

Consequence

DHRS4L2
NM_198083.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.774

Publications

0 publications found

Variant links:

Genes affected

DHRS4L2 (HGNC:19731): (dehydrogenase/reductase 4 like 2) This gene encodes a member of the short chain dehydrogenase reductase family. The encoded protein may be an NADPH dependent retinol oxidoreductase. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2010]

DHRS4L2 links:

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

DHRS4-AS1 links:

DHRS4L1 (HGNC:):

DHRS4L1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018613487).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198083.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DHRS4L2	NM_198083.4	MANE Select	c.40C>G	p.Arg14Gly	missense	Exon 1 of 8	NP_932349.2	Q6PKH6-1
DHRS4L2	NM_001193635.1		c.45-1195C>G		intron	N/A	NP_001180564.1	D5KJA1
DHRS4L2	NM_001193636.1		c.-175-1195C>G		intron	N/A	NP_001180565.1	A0A087WSZ6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DHRS4L2	ENST00000335125.11	TSL:1 MANE Select	c.40C>G	p.Arg14Gly	missense	Exon 1 of 8	ENSP00000334801.6	Q6PKH6-1
DHRS4L2	ENST00000559411.5	TSL:5	c.40C>G	p.Arg14Gly	missense	Exon 1 of 7	ENSP00000453889.1	Q6PKH6-2
DHRS4L2	ENST00000870060.1		c.40C>G	p.Arg14Gly	missense	Exon 1 of 8	ENSP00000540119.1

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

151826

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000962

GnomAD2 exomes

AF:

0.0000404

AC:

AN:

247648

AF XY:

0.0000224

show subpopulations

Gnomad AFR exome

AF:

0.000315

Gnomad AMR exome

AF:

0.0000582

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000892

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1459466

Hom.:

Cov.:

AF XY:

0.0000262

AC XY:

AN XY:

725856

show subpopulations

African (AFR)

AF:

0.000448

AC:

AN:

33452

American (AMR)

AF:

0.000291

AC:

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

85864

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52974

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

1110702

Other (OTH)

AF:

0.0000995

AC:

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000263

AC:

AN:

151944

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.000482

AC:

AN:

41500

American (AMR)

AF:

0.00111

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67900

Other (OTH)

AF:

0.000951

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.000529

ExAC

AF:

0.0000412

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.016

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.18

M_CAP

Benign

0.012

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.91

PhyloP100

0.77

PROVEAN

Benign

-0.80

REVEL

Benign

0.13

Sift

Benign

0.34

Sift4G

Benign

0.42

Polyphen

0.0

Vest4

0.24

MVP

0.23

MPC

0.043

ClinPred

0.0097

GERP RS

0.44

PromoterAI

-0.11

Neutral

(source)

gMVP

0.40

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over