rs4394668

Variant names:

• chr1-12611224-T-C
• rs4394668
• NM_004753.7:c.195+5930A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-12611224-T-C
• chr1-12611224-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004753.7(DHRS3):​c.195+5930A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,012 control chromosomes in the GnomAD database, including 3,223 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3223 hom., cov: 33)
• Consequence: DHRS3 NM_004753.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 9 publications found

Genes affected

DHRS3 (HGNC:17693): (dehydrogenase/reductase 3) Predicted to enable NAD-retinol dehydrogenase activity. Predicted to be involved in regulation of retinoic acid receptor signaling pathway and retinoid metabolic process. Predicted to act upstream of or within several processes, including animal organ morphogenesis; negative regulation of retinoic acid receptor signaling pathway; and regulation of ossification. Predicted to be located in endoplasmic reticulum membrane and photoreceptor outer segment membrane. Predicted to be active in lipid droplet. [provided by Alliance of Genome Resources, Apr 2022]

DHRS3 Gene-Disease associations (from GenCC):

• craniosynostosis

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ENSG00000305650 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHRS3	NM_004753.7	c.195+5930A>G		intron_variant	Intron 1 of 5	ENST00000616661.5	NP_004744.2
DHRS3	XM_047434406.1	c.-10849A>G		5_prime_UTR_variant	Exon 1 of 6		XP_047290362.1
DHRS3	NM_001319225.2	c.-61+5336A>G		intron_variant	Intron 1 of 5		NP_001306154.1
DHRS3	XM_006711036.3	c.195+5930A>G		intron_variant	Intron 1 of 3		XP_006711099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHRS3	ENST00000616661.5	c.195+5930A>G		intron_variant	Intron 1 of 5	1	NM_004753.7	ENSP00000480439.1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30483 AN: 151894 Hom.: 3216 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.205

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.201 AC: 30504 AN: 152012 Hom.: 3223 Cov.: 33 AF XY: 0.201 AC XY: 14936 AN XY: 74310

African (AFR) AF: 0.161 AC: 6659 AN: 41458

American (AMR) AF: 0.193 AC: 2954 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 731 AN: 3466

East Asian (EAS) AF: 0.370 AC: 1910 AN: 5164

South Asian (SAS) AF: 0.185 AC: 890 AN: 4818

European-Finnish (FIN) AF: 0.248 AC: 2620 AN: 10548

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14072 AN: 67970

Other (OTH) AF: 0.213 AC: 448 AN: 2108

Alfa AF: 0.204 Hom.: 14757

Bravo AF: 0.199

Asia WGS AF: 0.279 AC: 968 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.24
DANN	Benign	0.24
PhyloP100		-1.3
Mutation Taster		=100/0	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: rs4394668; hg19: chr1-12671229;