NM_198083.4:c.16C>T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_198083.4(DHRS4L2):​c.16C>T​(p.Leu6Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L6L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DHRS4L2 NM_198083.4 synonymous
• Clinical Significance: Not reported in ClinVar
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=-0.294 with no splicing effect.

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>T	p.Leu6Leu	synonymous	Exon 1 of 8	NP_932349.2	Q6PKH6-1
	DHRS4L2	NM_001193635.1		c.45-1219C>T		intron	N/A	NP_001180564.1	D5KJA1
	DHRS4L2	NM_001193636.1		c.-175-1219C>T		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>T	p.Leu6Leu	synonymous	Exon 1 of 8	ENSP00000334801.6	Q6PKH6-1
	DHRS4L2	ENST00000559411.5	TSL:5	c.16C>T	p.Leu6Leu	synonymous	Exon 1 of 7	ENSP00000453889.1	Q6PKH6-2
	DHRS4L2	ENST00000870060.1		c.16C>T	p.Leu6Leu	synonymous	Exon 1 of 8	ENSP00000540119.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460226 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 726328

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.0000224 AC: 1 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: 0.0000116 AC: 1 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 Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.1
DANN	Benign	0.78
PhyloP100		-0.29
PromoterAI		-0.25	Neutral

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;