rs2277532

Variant names:

• chr15-42952501-A-G
• rs2277532
• NM_174916.3:c.4836-53T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-42952501-A-G
• chr15-42952501-A-C
• chr15-42952501-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_174916.3(UBR1):​c.4836-53T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 1,592,614 control chromosomes in the GnomAD database, including 360,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (27248 hom., cov: 32)
  • Exomes 𝑓: 0.67 (333118 hom.)
• Consequence: UBR1 NM_174916.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.00
• Publications: 17 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 15-42952501-A-G is Benign according to our data. Variant chr15-42952501-A-G is described in ClinVar as Benign. ClinVar VariationId is 1180324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174916.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR1	NM_174916.3	MANE Select	c.4836-53T>C		intron	N/A	NP_777576.1	Q8IWV7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR1	ENST00000290650.9	TSL:1 MANE Select	c.4836-53T>C		intron	N/A	ENSP00000290650.4	Q8IWV7-1
	UBR1	ENST00000914218.1		c.4908-53T>C		intron	N/A	ENSP00000584277.1
	UBR1	ENST00000914217.1		c.4812-53T>C		intron	N/A	ENSP00000584276.1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83990 AN: 152032 Hom.: 27250 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.607

GnomAD4 exome AF: 0.674 AC: 970725 AN: 1440464 Hom.: 333118 AF XY: 0.671 AC XY: 481843 AN XY: 718098

African (AFR) AF: 0.169 AC: 5555 AN: 32820

American (AMR) AF: 0.716 AC: 31963 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 16840 AN: 25992

East Asian (EAS) AF: 0.603 AC: 23877 AN: 39584

South Asian (SAS) AF: 0.543 AC: 46559 AN: 85728

European-Finnish (FIN) AF: 0.704 AC: 37165 AN: 52776

Middle Eastern (MID) AF: 0.612 AC: 3505 AN: 5730

European-Non Finnish (NFE) AF: 0.701 AC: 766366 AN: 1093530

Other (OTH) AF: 0.652 AC: 38895 AN: 59662

GnomAD4 genome AF: 0.552 AC: 83995 AN: 152150 Hom.: 27248 Cov.: 32 AF XY: 0.555 AC XY: 41239 AN XY: 74350

African (AFR) AF: 0.189 AC: 7869 AN: 41526

American (AMR) AF: 0.688 AC: 10518 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2240 AN: 3468

East Asian (EAS) AF: 0.623 AC: 3225 AN: 5180

South Asian (SAS) AF: 0.560 AC: 2701 AN: 4820

European-Finnish (FIN) AF: 0.699 AC: 7382 AN: 10568

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.705 AC: 47936 AN: 67978

Other (OTH) AF: 0.603 AC: 1276 AN: 2116

Alfa AF: 0.649 Hom.: 103871

Bravo AF: 0.535

Asia WGS AF: 0.557 AC: 1937 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.4
DANN	Benign	0.63
PhyloP100		-1.0
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2277532;

hg19: chr15-43244699;

COSMIC: COSV51927704;

COSMIC: COSV51927704;