rs10518694

chr15-52780476-C-A

Variant summary

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

The NM_004498.4(ONECUT1):c.1105+8304G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 989,630 control chromosomes in the GnomAD database, including 10,022 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 0.14 (1541 hom., cov: 33)
  • Exomes 𝑓: 0.14 (8481 hom.)
• Consequence: ONECUT1 NM_004498.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.871

Genes affected

ONECUT1 (HGNC:8138): (one cut homeobox 1) This gene encodes a member of the Cut homeobox family of transcription factors. Expression of the encoded protein is enriched in the liver, where it stimulates transcription of liver-expressed genes, and antagonizes glucocorticoid-stimulated gene transcription. This gene may influence a variety of cellular processes including glucose metabolism, cell cycle regulation, and it may also be associated with cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ONECUT1	NM_004498.4	c.1105+8304G>T		intron_variant		ENST00000305901.7
ONECUT1	NR_073510.2	n.289+120G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ONECUT1	ENST00000305901.7	c.1105+8304G>T		intron_variant		1	NM_004498.4	P1
ONECUT1	ENST00000560699.2	n.588+120G>T		intron_variant, non_coding_transcript_variant		3
ONECUT1	ENST00000561401.3	n.50+10553G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21512 AN: 151998 Hom.: 1543 Cov.: 33

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.139 AC: 116063 AN: 837514 Hom.: 8481 AF XY: 0.139 AC XY: 58556 AN XY: 421332

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.136

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.193

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.108

Gnomad4 NFE exome AF: 0.137

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.141 AC: 21522 AN: 152116 Hom.: 1541 Cov.: 33 AF XY: 0.141 AC XY: 10462 AN XY: 74368

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.128

Alfa AF: 0.141 Hom.: 564

Bravo AF: 0.143

Asia WGS AF: 0.194 AC: 674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	17
Dann	Benign	0.74

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: rs10518694; hg19: chr15-53072673;