14-23988963-C-G

Variant names:

• chr14-23988963-C-G
• rs374580169
• NM_198083.4:c.16C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_198083.4(DHRS4L2):​c.16C>G​(p.Leu6Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,612,092 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Synonymous variant affecting the same amino acid position (i.e. L6L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: DHRS4L2 NM_198083.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.294
• Publications: 0 publications found

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]

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

DHRS4L1 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09684625).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHRS4L2	NM_198083.4	MANE Select	c.16C>G	p.Leu6Val	missense	Exon 1 of 8	NP_932349.2	Q6PKH6-1
	DHRS4L2	NM_001193635.1		c.45-1219C>G		intron	N/A	NP_001180564.1	D5KJA1
	DHRS4L2	NM_001193636.1		c.-175-1219C>G		intron	N/A	NP_001180565.1	A0A087WSZ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHRS4L2	ENST00000335125.11	TSL:1 MANE Select	c.16C>G	p.Leu6Val	missense	Exon 1 of 8	ENSP00000334801.6	Q6PKH6-1
	DHRS4L2	ENST00000559411.5	TSL:5	c.16C>G	p.Leu6Val	missense	Exon 1 of 7	ENSP00000453889.1	Q6PKH6-2
	DHRS4L2	ENST00000870060.1		c.16C>G	p.Leu6Val	missense	Exon 1 of 8	ENSP00000540119.1

Frequencies

GnomAD3 genomes AF: 0.0000593 AC: 9 AN: 151866 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000803 AC: 2 AN: 249196 AF XY: 0.00000742

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1460226 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 726328

African (AFR) AF: 0.000239 AC: 8 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 85990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111256

Other (OTH) AF: 0.00 AC: 0 AN: 60332

GnomAD4 genome AF: 0.0000593 AC: 9 AN: 151866 Hom.: 0 Cov.: 33 AF XY: 0.0000539 AC XY: 4 AN XY: 74150

African (AFR) AF: 0.000217 AC: 9 AN: 41386

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67926

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000756

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	11
DANN	Benign	0.90
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-0.61	T
PhyloP100		-0.29
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.074
Sift	Benign	0.073	T
Sift4G	Benign	0.33	T
Polyphen		0.43	B
Vest4		0.12
MVP		0.77
MPC		0.039
ClinPred		0.027	T
GERP RS		-0.29
PromoterAI		-0.10	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.46
Mutation Taster		=98/2	polymorphism

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: rs374580169; hg19: chr14-24458172;