rs2412747

Variant names:

• chr15-42994605-T-C
• rs2412747
• NM_174916.3:c.3757+3563A>G

Variant summary

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

The NM_174916.3(UBR1):​c.3757+3563A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 152,112 control chromosomes in the GnomAD database, including 48,830 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 0.79 (48830 hom., cov: 32)
• Consequence: UBR1 NM_174916.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 3 publications found

Genes affected

UBR1 (HGNC:16808): (ubiquitin protein ligase E3 component n-recognin 1) The N-end rule pathway is one proteolytic pathway of the ubiquitin system. The recognition component of this pathway, encoded by this gene, binds to a destabilizing N-terminal residue of a substrate protein and participates in the formation of a substrate-linked multiubiquitin chain. This leads to the eventual degradation of the substrate protein. The protein described in this record has a RING-type zinc finger and a UBR-type zinc finger. Mutations in this gene have been associated with Johanson-Blizzard syndrome. [provided by RefSeq, Jul 2008]

UBR1 Gene-Disease associations (from GenCC):

• Johanson-Blizzard syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBR1	NM_174916.3	c.3757+3563A>G		intron_variant	Intron 33 of 46	ENST00000290650.9	NP_777576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBR1	ENST00000290650.9	c.3757+3563A>G		intron_variant	Intron 33 of 46	1	NM_174916.3	ENSP00000290650.4
UBR1	ENST00000566493.1	n.32+3563A>G		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120187 AN: 151994 Hom.: 48827 Cov.: 32

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.836

Gnomad ASJ AF: 0.899

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.881

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.885

Gnomad OTH AF: 0.815

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

GnomAD4 genome AF: 0.790 AC: 120222 AN: 152112 Hom.: 48830 Cov.: 32 AF XY: 0.793 AC XY: 58961 AN XY: 74354

African (AFR) AF: 0.578 AC: 23957 AN: 41452

American (AMR) AF: 0.836 AC: 12765 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.899 AC: 3121 AN: 3470

East Asian (EAS) AF: 0.774 AC: 4017 AN: 5188

South Asian (SAS) AF: 0.880 AC: 4252 AN: 4832

European-Finnish (FIN) AF: 0.873 AC: 9229 AN: 10572

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.885 AC: 60182 AN: 68002

Other (OTH) AF: 0.809 AC: 1711 AN: 2114

Alfa AF: 0.817 Hom.: 7858

Bravo AF: 0.775

Asia WGS AF: 0.775 AC: 2693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.69
PhyloP100		-0.15
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: rs2412747; hg19: chr15-43286803;