rs4568

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHRS1	NM_001136050.3	c.*56C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000288111.12	NP_001129522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHRS1	ENST00000288111	c.*56C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_001136050.3	ENSP00000288111.7

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

Gnomad4 AFR exome AF: 0.332

Gnomad4 AMR exome AF: 0.286

Gnomad4 ASJ exome AF: 0.313

Gnomad4 EAS exome AF: 0.729

Gnomad4 SAS exome AF: 0.502

Gnomad4 FIN exome AF: 0.349

Gnomad4 NFE exome AF: 0.252

Gnomad4 OTH exome AF: 0.306

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

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.306

Alfa AF: 0.274 Hom.: 12781

Bravo AF: 0.306

Asia WGS AF: 0.617 AC: 2144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.37

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: rs4568; hg19: chr14-24760009; COSMIC: COSV55384255; COSMIC: COSV55384255;