15-52780476-C-T

Variant names:

• chr15-52780476-C-T
• rs10518694
• NM_004498.4:c.1105+8304G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004498.4(ONECUT1):​c.1105+8304G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000238 in 839,044 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: ONECUT1 NM_004498.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.871
• Publications: 0 publications found

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]

ONECUT1 Gene-Disease associations (from GenCC):

• neonatal diabetes mellitus

  Inheritance: AR Classification: STRONG Submitted by: G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ONECUT1	NM_004498.4	c.1105+8304G>A		intron_variant	Intron 1 of 1	ENST00000305901.7	NP_004489.1
ONECUT1	NR_073510.2	n.289+120G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ONECUT1	ENST00000305901.7	c.1105+8304G>A		intron_variant	Intron 1 of 1	1	NM_004498.4	ENSP00000302630.4
ONECUT1	ENST00000560699.2	n.588+120G>A		intron_variant	Intron 1 of 1	3
ONECUT1	ENST00000561401.3	n.50+10553G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000238 AC: 2 AN: 839044 Hom.: 0 AF XY: 0.00000237 AC XY: 1 AN XY: 422108

African (AFR) AF: 0.00 AC: 0 AN: 19248

American (AMR) AF: 0.00 AC: 0 AN: 19536

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17580

East Asian (EAS) AF: 0.00 AC: 0 AN: 30652

South Asian (SAS) AF: 0.00 AC: 0 AN: 52974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4164

European-Non Finnish (NFE) AF: 0.00000319 AC: 2 AN: 626138

Other (OTH) AF: 0.00 AC: 0 AN: 38622

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Benign	0.73
PhyloP100		0.87
Mutation Taster		=100/0	polymorphism

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: rs10518694; hg19: chr15-53072673;