rs3745064

Variant names:

• chr18-57486834-A-G
• rs3745064
• NM_004852.3:c.*10111A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004852.3(ONECUT2):​c.*10111A>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.52 in 152,518 control chromosomes in the GnomAD database, including 23,795 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 0.52 (23699 hom., cov: 32)
  • Exomes 𝑓: 0.66 (96 hom.)
• Consequence: ONECUT2 NM_004852.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.74
• Publications: 6 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.679 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ONECUT2	NM_004852.3	MANE Select	c.*10111A>G		3_prime_UTR	Exon 2 of 2	NP_004843.2	O95948

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ONECUT2	ENST00000491143.3	TSL:1 MANE Select	c.*10111A>G		3_prime_UTR	Exon 2 of 2	ENSP00000419185.2	O95948

Frequencies

GnomAD3 genomes AF: 0.520 AC: 79047 AN: 151966 Hom.: 23709 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.533

GnomAD4 exome AF: 0.657 AC: 285 AN: 434 Hom.: 96 Cov.: 0 AF XY: 0.630 AC XY: 165 AN XY: 262

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.657 AC: 281 AN: 428

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.520 AC: 79029 AN: 152084 Hom.: 23699 Cov.: 32 AF XY: 0.515 AC XY: 38283 AN XY: 74334

African (AFR) AF: 0.210 AC: 8713 AN: 41504

American (AMR) AF: 0.491 AC: 7499 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2455 AN: 3470

East Asian (EAS) AF: 0.517 AC: 2672 AN: 5168

South Asian (SAS) AF: 0.592 AC: 2847 AN: 4812

European-Finnish (FIN) AF: 0.608 AC: 6411 AN: 10552

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46519 AN: 67992

Other (OTH) AF: 0.535 AC: 1130 AN: 2112

Alfa AF: 0.623 Hom.: 39618

Bravo AF: 0.494

Asia WGS AF: 0.552 AC: 1918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Benign	0.86
PhyloP100		3.7
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: rs3745064; hg19: chr18-55154066; COSMIC: COSV72203399;