rs674849

chr18-57479654-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004852.3(ONECUT2):c.*2931C>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 0.335 in 152,482 control chromosomes in the GnomAD database, including 9,064 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 0.33 (9048 hom., cov: 32)
  • Exomes 𝑓: 0.28 (16 hom.)
• Consequence: ONECUT2 NM_004852.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.53

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ONECUT2	NM_004852.3	c.*2931C>T		3_prime_UTR_variant	2/2	ENST00000491143.3
ONECUT2	XM_047437947.1	c.*3142C>T		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ONECUT2	ENST00000491143.3	c.*2931C>T		3_prime_UTR_variant	2/2	1	NM_004852.3	P1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50854 AN: 151918 Hom.: 9027 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.337

GnomAD4 exome AF: 0.283 AC: 127 AN: 448 Hom.: 16 Cov.: 0 AF XY: 0.293 AC XY: 79 AN XY: 270

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.279

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.335 AC: 50926 AN: 152034 Hom.: 9048 Cov.: 32 AF XY: 0.337 AC XY: 25075 AN XY: 74302

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.338

Alfa AF: 0.302 Hom.: 3551

Bravo AF: 0.332

Asia WGS AF: 0.274 AC: 954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	10
Dann	Benign	0.79

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: rs674849; hg19: chr18-55146886; COSMIC: COSV72153125; COSMIC: COSV72153125;