rs4568

Variant names:

• chr14-24290803-G-A
• rs4568
• NM_001136050.3:c.*56C>T

Variant summary

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

The NM_001136050.3(DHRS1):​c.*56C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,604,948 control chromosomes in the GnomAD database, including 76,649 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 0.31 (7953 hom., cov: 29)
  • Exomes 𝑓: 0.29 (68696 hom.)
• Consequence: DHRS1 NM_001136050.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.415
• Publications: 35 publications found

Genes affected

DHRS1 (HGNC:16445): (dehydrogenase/reductase 1) This gene encodes a member of the short-chain dehydrogenases/reductases (SDR) family. The encoded enzyme contains a conserved catalytic domain and likely functions as an oxidoreductase. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Nov 2008]

NOP9 (HGNC:19826): (NOP9 nucleolar protein) Enables RNA binding activity. Predicted to be involved in ribosome biogenesis. Predicted to be part of 90S preribosome and preribosome, small subunit precursor. Predicted to be active in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000288044 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136050.3. 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
	DHRS1	NM_001136050.3	MANE Select	c.*56C>T		3_prime_UTR	Exon 9 of 9	NP_001129522.1	Q96LJ7
	DHRS1	NM_138452.3		c.*56C>T		3_prime_UTR	Exon 9 of 9	NP_612461.1	Q96LJ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHRS1	ENST00000288111.12	TSL:1 MANE Select	c.*56C>T		3_prime_UTR	Exon 9 of 9	ENSP00000288111.7	Q96LJ7
	DHRS1	ENST00000561281.4	TSL:1	n.976C>T		non_coding_transcript_exon	Exon 2 of 2
	DHRS1	ENST00000396813.5	TSL:2	c.*56C>T		3_prime_UTR	Exon 9 of 9	ENSP00000380027.1	Q96LJ7

Frequencies

GnomAD3 genomes AF: 0.311 AC: 46954 AN: 150944 Hom.: 7952 Cov.: 29

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.300

GnomAD4 exome AF: 0.290 AC: 421357 AN: 1453886 Hom.: 68696 Cov.: 31 AF XY: 0.296 AC XY: 214114 AN XY: 723098

African (AFR) AF: 0.332 AC: 11065 AN: 33312

American (AMR) AF: 0.286 AC: 12741 AN: 44534

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 8087 AN: 25860

East Asian (EAS) AF: 0.729 AC: 28890 AN: 39616

South Asian (SAS) AF: 0.502 AC: 43088 AN: 85836

European-Finnish (FIN) AF: 0.349 AC: 18551 AN: 53220

Middle Eastern (MID) AF: 0.325 AC: 1790 AN: 5512

European-Non Finnish (NFE) AF: 0.252 AC: 278739 AN: 1105912

Other (OTH) AF: 0.306 AC: 18406 AN: 60084

GnomAD4 genome AF: 0.311 AC: 46978 AN: 151062 Hom.: 7953 Cov.: 29 AF XY: 0.323 AC XY: 23842 AN XY: 73750

African (AFR) AF: 0.335 AC: 13767 AN: 41116

American (AMR) AF: 0.275 AC: 4169 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1040 AN: 3464

East Asian (EAS) AF: 0.709 AC: 3591 AN: 5068

South Asian (SAS) AF: 0.518 AC: 2444 AN: 4716

European-Finnish (FIN) AF: 0.355 AC: 3694 AN: 10398

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17225 AN: 67824

Other (OTH) AF: 0.306 AC: 643 AN: 2100

Alfa AF: 0.279 Hom.: 28913

Bravo AF: 0.306

Asia WGS AF: 0.617 AC: 2144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.37
PhyloP100		-0.41
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: rs4568; hg19: chr14-24760009; COSMIC: COSV55384255; COSMIC: COSV55384255;