rs8107449

chr19-4933765-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
UHRF1	NM_001048201.3	c.785+809G>A		intron_variant		ENST00000650932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UHRF1	ENST00000650932.1	c.785+809G>A		intron_variant			NM_001048201.3	P2

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

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.0116

Gnomad4 SAS AF: 0.0672

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.166

Alfa AF: 0.190 Hom.: 1815

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

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: rs8107449; hg19: chr19-4933777;