rs8107449

Variant names:

• chr19-4933765-G-A
• rs8107449
• NM_001048201.3:c.785+809G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001048201.3(UHRF1):​c.785+809G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,076 control chromosomes in the GnomAD database, including 2,221 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 0.16 (2221 hom., cov: 32)
• Consequence: UHRF1 NM_001048201.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 2 publications found

Genes affected

UHRF1 (HGNC:12556): (ubiquitin like with PHD and ring finger domains 1) This gene encodes a member of a subfamily of RING-finger type E3 ubiquitin ligases. The protein binds to specific DNA sequences, and recruits a histone deacetylase to regulate gene expression. Its expression peaks at late G1 phase and continues during G2 and M phases of the cell cycle. It plays a major role in the G1/S transition by regulating topoisomerase IIalpha and retinoblastoma gene expression, and functions in the p53-dependent DNA damage checkpoint. It is regarded as a hub protein for the integration of epigenetic information. This gene is up-regulated in various cancers, and it is therefore considered to be a therapeutic target. Multiple transcript variants encoding different isoforms have been found for this gene. A related pseudogene exists on chromosome 12. [provided by RefSeq, Feb 2014]

UHRF1 Gene-Disease associations (from GenCC):

• immunodeficiency-centromeric instability-facial anomalies syndrome

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UHRF1	NM_001048201.3	c.785+809G>A		intron_variant	Intron 5 of 16	ENST00000650932.1	NP_001041666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UHRF1	ENST00000650932.1	c.785+809G>A		intron_variant	Intron 5 of 16		NM_001048201.3	ENSP00000498698.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24990 AN: 151958 Hom.: 2220 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.0116

Gnomad SAS AF: 0.0674

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.168

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.164 AC: 24998 AN: 152076 Hom.: 2221 Cov.: 32 AF XY: 0.158 AC XY: 11739 AN XY: 74330

African (AFR) AF: 0.134 AC: 5550 AN: 41500

American (AMR) AF: 0.179 AC: 2730 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 631 AN: 3472

East Asian (EAS) AF: 0.0116 AC: 60 AN: 5172

South Asian (SAS) AF: 0.0672 AC: 324 AN: 4820

European-Finnish (FIN) AF: 0.144 AC: 1519 AN: 10570

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13717 AN: 67976

Other (OTH) AF: 0.166 AC: 349 AN: 2108

Alfa AF: 0.182 Hom.: 3460

Bravo AF: 0.164

Asia WGS AF: 0.0430 AC: 150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.44
DANN	Benign	0.96
PhyloP100		-1.9

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: rs8107449; hg19: chr19-4933777;