rs2054389

Variant names:

• chr15-42963923-T-A
• rs2054389
• NM_174916.3:c.4700+12A>T

Your query was ambiguous. Multiple possible variants found:

• chr15-42963923-T-A
• chr15-42963923-T-C

Variant summary

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

The NM_174916.3(UBR1):​c.4700+12A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,416,014 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: 29)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: UBR1 NM_174916.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.53
• Publications: 11 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: 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=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBR1	NM_174916.3	c.4700+12A>T		intron_variant	Intron 42 of 46	ENST00000290650.9	NP_777576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBR1	ENST00000290650.9	c.4700+12A>T		intron_variant	Intron 42 of 46	1	NM_174916.3	ENSP00000290650.4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1416014 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 707584

African (AFR) AF: 0.00 AC: 0 AN: 32492

American (AMR) AF: 0.00 AC: 0 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25868

East Asian (EAS) AF: 0.00 AC: 0 AN: 39408

South Asian (SAS) AF: 0.00 AC: 0 AN: 85292

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53250

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 9.34e-7 AC: 1 AN: 1070512

Other (OTH) AF: 0.00 AC: 0 AN: 58864

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 6615

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.25
DANN	Benign	0.52
PhyloP100		-2.5

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: rs2054389; hg19: chr15-43256121;