rs4394668

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
DHRS3	NM_004753.7	c.195+5930A>G		intron_variant		ENST00000616661.5	NP_004744.2
DHRS3	XM_047434406.1	c.-10849A>G		5_prime_UTR_variant	1/6		XP_047290362.1
DHRS3	NM_001319225.2	c.-61+5336A>G		intron_variant			NP_001306154.1
DHRS3	XM_006711036.3	c.195+5930A>G		intron_variant			XP_006711099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHRS3	ENST00000616661.5	c.195+5930A>G		intron_variant		1	NM_004753.7	ENSP00000480439	P1
DHRS3	ENST00000464917.5	c.-61+5336A>G		intron_variant		3		ENSP00000478218
DHRS3	ENST00000482265.1	n.137+5336A>G		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.213

Alfa AF: 0.203 Hom.: 6951

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

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

Other links and lift over

dbSNP: rs4394668; hg19: chr1-12671229;