18-57488479-C-G

Variant names:

• chr18-57488479-C-G
• rs608017
• NM_004852.3:c.*11756C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004852.3(ONECUT2):​c.*11756C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,396 control chromosomes in the GnomAD database, including 11,839 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 (11811 hom., cov: 32)
  • Exomes 𝑓: 0.34 (28 hom.)
• Consequence: ONECUT2 NM_004852.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• 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 rank	MANE	Protein	UniProt
ONECUT2	NM_004852.3	c.*11756C>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000491143.3	NP_004843.2
ONECUT2	XM_047437947.1	c.*11967C>G		3_prime_UTR_variant	Exon 3 of 3		XP_047293903.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ONECUT2	ENST00000491143.3	c.*11756C>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_004852.3	ENSP00000419185.2

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58500 AN: 151846 Hom.: 11773 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.388

GnomAD4 exome AF: 0.345 AC: 149 AN: 432 Hom.: 28 Cov.: 0 AF XY: 0.373 AC XY: 97 AN XY: 260

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: 0.345 AC: 147 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

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

GnomAD4 genome AF: 0.386 AC: 58598 AN: 151964 Hom.: 11811 Cov.: 32 AF XY: 0.395 AC XY: 29318 AN XY: 74270

African (AFR) AF: 0.473 AC: 19603 AN: 41418

American (AMR) AF: 0.464 AC: 7095 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1009 AN: 3468

East Asian (EAS) AF: 0.484 AC: 2499 AN: 5168

South Asian (SAS) AF: 0.407 AC: 1963 AN: 4826

European-Finnish (FIN) AF: 0.392 AC: 4132 AN: 10538

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.310 AC: 21068 AN: 67950

Other (OTH) AF: 0.387 AC: 817 AN: 2110

Alfa AF: 0.229 Hom.: 551

Bravo AF: 0.396

Asia WGS AF: 0.427 AC: 1485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.61
DANN	Benign	0.64
PhyloP100		-0.24
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: rs608017; hg19: chr18-55155711; COSMIC: COSV72203365;