chr18-57482122-C-T

Variant names:

• chr18-57482122-C-T
• rs615030
• NM_004852.3:c.*5399C>T

Variant summary

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

The NM_004852.3(ONECUT2):​c.*5399C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,916 control chromosomes in the GnomAD database, including 11,592 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 0.38 (11592 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ONECUT2 NM_004852.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197
• Publications: 8 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ONECUT2	NM_004852.3	c.*5399C>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000491143.3	NP_004843.2
ONECUT2	XM_047437947.1	c.*5610C>T		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.*5399C>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_004852.3	ENSP00000419185.2

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57851 AN: 151796 Hom.: 11550 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.385

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.382 AC: 57959 AN: 151916 Hom.: 11592 Cov.: 32 AF XY: 0.391 AC XY: 29015 AN XY: 74236

African (AFR) AF: 0.473 AC: 19573 AN: 41424

American (AMR) AF: 0.464 AC: 7081 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1007 AN: 3466

East Asian (EAS) AF: 0.483 AC: 2489 AN: 5158

South Asian (SAS) AF: 0.405 AC: 1948 AN: 4810

European-Finnish (FIN) AF: 0.389 AC: 4094 AN: 10516

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

European-Non Finnish (NFE) AF: 0.302 AC: 20542 AN: 67952

Other (OTH) AF: 0.384 AC: 812 AN: 2114

Alfa AF: 0.330 Hom.: 14424

Bravo AF: 0.392

Asia WGS AF: 0.427 AC: 1485 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.2
DANN	Benign	0.61
PhyloP100		0.20
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: rs615030; hg19: chr18-55149354;