rs608823

Positions:

• chr18-57488638-G-A
• chr18-57488638-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004852.3(ONECUT2):​c.*11915G>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.385 in 152,566 control chromosomes in the GnomAD database, including 11,858 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 0.39 (11830 hom., cov: 33)
  • Exomes 𝑓: 0.35 (28 hom.)
• Consequence: ONECUT2 NM_004852.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.89

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ONECUT2	NM_004852.3	c.*11915G>A		3_prime_UTR_variant	2/2	ENST00000491143.3
ONECUT2	XM_047437947.1	c.*12126G>A		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ONECUT2	ENST00000491143.3	c.*11915G>A		3_prime_UTR_variant	2/2	1	NM_004852.3	P1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58551 AN: 152014 Hom.: 11792 Cov.: 33

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.387

GnomAD4 exome AF: 0.346 AC: 150 AN: 434 Hom.: 28 Cov.: 0 AF XY: 0.374 AC XY: 98 AN XY: 262

Gnomad4 FIN exome AF: 0.345

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.386 AC: 58649 AN: 152132 Hom.: 11830 Cov.: 33 AF XY: 0.395 AC XY: 29346 AN XY: 74364

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.386

Alfa AF: 0.327 Hom.: 13926

Bravo AF: 0.396

Asia WGS AF: 0.428 AC: 1488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Benign	0.87

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: rs608823; hg19: chr18-55155870; COSMIC: COSV72203368;