chr15-42945005-T-C

Position:

• chr15-42945005-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
UBR1	NM_174916.3	c.*324A>G		3_prime_UTR_variant	47/47	ENST00000290650.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBR1	ENST00000290650.9	c.*324A>G		3_prime_UTR_variant	47/47	1	NM_174916.3	P1

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

Gnomad4 AFR exome AF: 0.645

Gnomad4 AMR exome AF: 0.847

Gnomad4 ASJ exome AF: 0.888

Gnomad4 EAS exome AF: 0.752

Gnomad4 SAS exome AF: 0.879

Gnomad4 FIN exome AF: 0.872

Gnomad4 NFE exome AF: 0.885

Gnomad4 OTH exome AF: 0.856

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

Gnomad4 AFR AF: 0.639

Gnomad4 AMR AF: 0.840

Gnomad4 ASJ AF: 0.897

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.881

Gnomad4 FIN AF: 0.873

Gnomad4 NFE AF: 0.885

Gnomad4 OTH AF: 0.821

Alfa AF: 0.869 Hom.: 94531

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.0
DANN	Benign	0.76

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: rs3803341; hg19: chr15-43237203;