rs3848516

Positions:

• chr18-57488148-A-G
• chr18-57488148-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004852.3(ONECUT2):​c.*11425A>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 0.522 in 152,530 control chromosomes in the GnomAD database, including 24,003 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 (23910 hom., cov: 33)
  • Exomes 𝑓: 0.66 (93 hom.)
• Consequence: ONECUT2 NM_004852.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.54

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ONECUT2	NM_004852.3	c.*11425A>G		3_prime_UTR_variant	2/2	ENST00000491143.3
ONECUT2	XM_047437947.1	c.*11636A>G		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ONECUT2	ENST00000491143.3	c.*11425A>G		3_prime_UTR_variant	2/2	1	NM_004852.3	P1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79383 AN: 151990 Hom.: 23921 Cov.: 33

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.536

GnomAD4 exome AF: 0.659 AC: 278 AN: 422 Hom.: 93 Cov.: 0 AF XY: 0.621 AC XY: 159 AN XY: 256

Gnomad4 FIN exome AF: 0.659

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.522 AC: 79364 AN: 152108 Hom.: 23910 Cov.: 33 AF XY: 0.517 AC XY: 38413 AN XY: 74352

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.708

Gnomad4 EAS AF: 0.516

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.688

Gnomad4 OTH AF: 0.537

Alfa AF: 0.609 Hom.: 10683

Bravo AF: 0.496

Asia WGS AF: 0.553 AC: 1921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.8
DANN	Benign	0.59

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: rs3848516; hg19: chr18-55155380;