chr15-42945005-T-C

Variant names:

• chr15-42945005-T-C
• rs3803341
• NM_174916.3:c.*324A>G

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.*324A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 334,876 control chromosomes in the GnomAD database, including 119,540 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.81 (50458 hom., cov: 31)
  • Exomes 𝑓: 0.87 (69082 hom.)
• Consequence: UBR1 NM_174916.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0960
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 15-42945005-T-C is Benign according to our data. Variant chr15-42945005-T-C is described in ClinVar as [Benign]. Clinvar id is 1226855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBR1	NM_174916.3	c.*324A>G		3_prime_UTR_variant	Exon 47 of 47	ENST00000290650.9	NP_777576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBR1	ENST00000290650.9	c.*324A>G		3_prime_UTR_variant	Exon 47 of 47	1	NM_174916.3	ENSP00000290650.4
UBR1	ENST00000562173.1	n.*182A>G		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122780 AN: 151988 Hom.: 50448 Cov.: 31

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.885

Gnomad OTH AF: 0.829

GnomAD4 exome AF: 0.867 AC: 158517 AN: 182770 Hom.: 69082 Cov.: 3 AF XY: 0.870 AC XY: 85540 AN XY: 98334

African (AFR) AF: 0.645 AC: 3444 AN: 5340

American (AMR) AF: 0.847 AC: 6297 AN: 7438

Ashkenazi Jewish (ASJ) AF: 0.888 AC: 4245 AN: 4778

East Asian (EAS) AF: 0.752 AC: 6064 AN: 8064

South Asian (SAS) AF: 0.879 AC: 28151 AN: 32024

European-Finnish (FIN) AF: 0.872 AC: 7514 AN: 8618

Middle Eastern (MID) AF: 0.869 AC: 577 AN: 664

European-Non Finnish (NFE) AF: 0.885 AC: 94162 AN: 106430

Other (OTH) AF: 0.856 AC: 8063 AN: 9414

GnomAD4 genome AF: 0.807 AC: 122822 AN: 152106 Hom.: 50458 Cov.: 31 AF XY: 0.809 AC XY: 60170 AN XY: 74370

African (AFR) AF: 0.639 AC: 26484 AN: 41462

American (AMR) AF: 0.840 AC: 12815 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.897 AC: 3113 AN: 3472

East Asian (EAS) AF: 0.769 AC: 3977 AN: 5174

South Asian (SAS) AF: 0.881 AC: 4250 AN: 4824

European-Finnish (FIN) AF: 0.873 AC: 9245 AN: 10590

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.885 AC: 60215 AN: 68006

Other (OTH) AF: 0.821 AC: 1731 AN: 2108

Alfa AF: 0.853 Hom.: 149704

Bravo AF: 0.795

Asia WGS AF: 0.766 AC: 2661 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.0
DANN	Benign	0.76
PhyloP100		-0.096
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: rs3803341; hg19: chr15-43237203;