NM_004498.4:c.1105+8304G>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004498.4. 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
	ONECUT1	NM_004498.4	MANE Select	c.1105+8304G>T		intron	N/A	NP_004489.1
	ONECUT1	NR_073510.2		n.289+120G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ONECUT1	ENST00000305901.7	TSL:1 MANE Select	c.1105+8304G>T		intron	N/A	ENSP00000302630.4
	ONECUT1	ENST00000560699.2	TSL:3	n.588+120G>T		intron	N/A
	ONECUT1	ENST00000561401.3	TSL:3	n.50+10553G>T		intron	N/A

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

African (AFR) AF: 0.147 AC: 2822 AN: 19222

American (AMR) AF: 0.136 AC: 2662 AN: 19512

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 2229 AN: 17556

East Asian (EAS) AF: 0.193 AC: 5910 AN: 30628

South Asian (SAS) AF: 0.141 AC: 7470 AN: 52876

European-Finnish (FIN) AF: 0.108 AC: 3239 AN: 30118

Middle Eastern (MID) AF: 0.117 AC: 486 AN: 4152

European-Non Finnish (NFE) AF: 0.137 AC: 85808 AN: 624890

Other (OTH) AF: 0.141 AC: 5437 AN: 38560

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

African (AFR) AF: 0.150 AC: 6215 AN: 41470

American (AMR) AF: 0.135 AC: 2066 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3470

East Asian (EAS) AF: 0.211 AC: 1093 AN: 5184

South Asian (SAS) AF: 0.144 AC: 691 AN: 4814

European-Finnish (FIN) AF: 0.102 AC: 1076 AN: 10576

Middle Eastern (MID) AF: 0.0925 AC: 27 AN: 292

European-Non Finnish (NFE) AF: 0.141 AC: 9604 AN: 67994

Other (OTH) AF: 0.128 AC: 271 AN: 2110

Alfa AF: 0.139 Hom.: 653

Bravo AF: 0.143

Asia WGS AF: 0.194 AC: 674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Benign	0.74
PhyloP100		0.87
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: rs10518694; hg19: chr15-53072673;