rs674849

Variant names:

• chr18-57479654-C-T
• rs674849
• NM_004852.3:c.*2931C>T

Variant summary

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

The ENST00000491143.3(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 ENST00000491143.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.53
• Publications: 5 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=-0.45).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000491143.3. 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.*2931C>T		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.*2931C>T		3_prime_UTR	Exon 2 of 2	ENSP00000419185.2

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

African (AFR) AF: 0.500 AC: 1 AN: 2

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: 0.279 AC: 119 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.375 AC: 6 AN: 16

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

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

African (AFR) AF: 0.453 AC: 18757 AN: 41446

American (AMR) AF: 0.292 AC: 4462 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 988 AN: 3472

East Asian (EAS) AF: 0.112 AC: 579 AN: 5166

South Asian (SAS) AF: 0.388 AC: 1866 AN: 4812

European-Finnish (FIN) AF: 0.324 AC: 3418 AN: 10544

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19742 AN: 67992

Other (OTH) AF: 0.338 AC: 714 AN: 2114

Alfa AF: 0.301 Hom.: 5485

Bravo AF: 0.332

Asia WGS AF: 0.274 AC: 954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	10
DANN	Benign	0.79
PhyloP100		3.5
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: rs674849; hg19: chr18-55146886; COSMIC: COSV72153125; COSMIC: COSV72153125;