rs519596

Variant names:

• chr18-57484633-G-A
• rs519596
• NM_004852.3:c.*7910G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004852.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ONECUT2	NM_004852.3	MANE Select	c.*7910G>A		3_prime_UTR	Exon 2 of 2	NP_004843.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ONECUT2	ENST00000491143.3	TSL:1 MANE Select	c.*7910G>A		3_prime_UTR	Exon 2 of 2	ENSP00000419185.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.311 AC: 23 AN: 74

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.350 AC: 7 AN: 20

Other (OTH) AF: 0.250 AC: 1 AN: 4

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

African (AFR) AF: 0.469 AC: 19429 AN: 41424

American (AMR) AF: 0.467 AC: 7128 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1010 AN: 3468

East Asian (EAS) AF: 0.484 AC: 2502 AN: 5168

South Asian (SAS) AF: 0.406 AC: 1956 AN: 4818

European-Finnish (FIN) AF: 0.392 AC: 4135 AN: 10542

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21325 AN: 67974

Other (OTH) AF: 0.391 AC: 823 AN: 2106

Alfa AF: 0.355 Hom.: 6756

Bravo AF: 0.397

Asia WGS AF: 0.429 AC: 1492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.085
DANN	Benign	0.41
PhyloP100		-0.71
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: rs519596; hg19: chr18-55151865;