rs615030

chr18-57482122-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004852.3(ONECUT2):c.*5399C>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 0.382 in 151,916 control chromosomes in the GnomAD database, including 11,592 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 0.38 (11592 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ONECUT2 NM_004852.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197

Genes affected

ONECUT2 (HGNC:8139): (one cut homeobox 2) This gene encodes a member of the onecut family of transcription factors, which are characterized by a cut domain and an atypical homeodomain. The protein binds to specific DNA sequences and stimulates expression of target genes, including genes involved in melanocyte and hepatocyte differentiation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ONECUT2	NM_004852.3	c.*5399C>T		3_prime_UTR_variant	2/2	ENST00000491143.3
ONECUT2	XM_047437947.1	c.*5610C>T		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ONECUT2	ENST00000491143.3	c.*5399C>T		3_prime_UTR_variant	2/2	1	NM_004852.3	P1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57851 AN: 151796 Hom.: 11550 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.385

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.382 AC: 57959 AN: 151916 Hom.: 11592 Cov.: 32 AF XY: 0.391 AC XY: 29015 AN XY: 74236

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.384

Alfa AF: 0.323 Hom.: 10779

Bravo AF: 0.392

Asia WGS AF: 0.427 AC: 1485 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	7.2
Dann	Benign	0.61

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: rs615030; hg19: chr18-55149354;