15-43065208-A-C

Variant names:

• chr15-43065208-A-C
• rs12050604
• NM_174916.3:c.798+2690T>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.798+2690T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,046 control chromosomes in the GnomAD database, including 27,071 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 0.54 (27071 hom., cov: 31)
• Consequence: UBR1 NM_174916.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBR1	NM_174916.3	c.798+2690T>G		intron_variant	Intron 6 of 46	ENST00000290650.9	NP_777576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBR1	ENST00000290650.9	c.798+2690T>G		intron_variant	Intron 6 of 46	1	NM_174916.3	ENSP00000290650.4
UBR1	ENST00000546274.6	c.798+2690T>G		intron_variant	Intron 6 of 28	2		ENSP00000477932.1
UBR1	ENST00000563239.1	n.*202+5691T>G		intron_variant	Intron 4 of 5	3		ENSP00000456502.1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82316 AN: 151928 Hom.: 27073 Cov.: 31

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.593

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

GnomAD4 genome AF: 0.541 AC: 82306 AN: 152046 Hom.: 27071 Cov.: 31 AF XY: 0.545 AC XY: 40469 AN XY: 74322

African (AFR) AF: 0.146 AC: 6055 AN: 41488

American (AMR) AF: 0.685 AC: 10450 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2234 AN: 3470

East Asian (EAS) AF: 0.623 AC: 3215 AN: 5158

South Asian (SAS) AF: 0.559 AC: 2694 AN: 4816

European-Finnish (FIN) AF: 0.699 AC: 7392 AN: 10572

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.709 AC: 48186 AN: 67966

Other (OTH) AF: 0.589 AC: 1242 AN: 2108

Alfa AF: 0.640 Hom.: 16336

Bravo AF: 0.524

Asia WGS AF: 0.553 AC: 1924 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.7
DANN	Benign	0.62
PhyloP100		0.17
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: rs12050604; hg19: chr15-43357406;