chr18-57484633-G-A

Position:

• chr18-57484633-G-A

Variant summary

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

The NM_004852.3(ONECUT2):​c.*7910G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,062 control chromosomes in the GnomAD database, including 11,834 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 (11831 hom., cov: 32)
  • Exomes 𝑓: 0.31 (3 hom.)
• Consequence: ONECUT2 NM_004852.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709

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=-0.89).
• 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	Protein	UniProt
ONECUT2	NM_004852.3	c.*7910G>A		3_prime_UTR_variant	2/2	ENST00000491143.3	NP_004843.2
ONECUT2	XM_047437947.1	c.*8121G>A		3_prime_UTR_variant	3/3		XP_047293903.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ONECUT2	ENST00000491143.3	c.*7910G>A		3_prime_UTR_variant	2/2	1	NM_004852.3	ENSP00000419185	P1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58611 AN: 151844 Hom.: 11787 Cov.: 32

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.392

GnomAD4 exome AF: 0.310 AC: 31 AN: 100 Hom.: 3 Cov.: 0 AF XY: 0.297 AC XY: 22 AN XY: 74

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.311

Gnomad4 NFE exome AF: 0.350

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.386 AC: 58721 AN: 151962 Hom.: 11831 Cov.: 32 AF XY: 0.395 AC XY: 29356 AN XY: 74270

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.391

Alfa AF: 0.351 Hom.: 4218

Bravo AF: 0.397

Asia WGS AF: 0.429 AC: 1492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.085
DANN	Benign	0.41

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: rs519596; hg19: chr18-55151865;