1-19173341-G-C

Variant names:

• chr1-19173341-G-C
• rs951908
• NM_020765.3:c.3166-35C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020765.3(UBR4):​c.3166-35C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 1,612,628 control chromosomes in the GnomAD database, including 320,500 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.67 (34732 hom., cov: 32)
  • Exomes 𝑓: 0.62 (285768 hom.)
• Consequence: UBR4 NM_020765.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.600
• Publications: 11 publications found

Genes affected

UBR4 (HGNC:30313): (ubiquitin protein ligase E3 component n-recognin 4) The protein encoded by this gene is an E3 ubiquitin-protein ligase that interacts with the retinoblastoma-associated protein in the nucleus and with calcium-bound calmodulin in the cytoplasm. The encoded protein appears to be a cytoskeletal component in the cytoplasm and part of the chromatin scaffold in the nucleus. In addition, this protein is a target of the human papillomavirus type 16 E7 oncoprotein. [provided by RefSeq, Aug 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBR4	NM_020765.3	c.3166-35C>G		intron_variant	Intron 23 of 105	ENST00000375254.8	NP_065816.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBR4	ENST00000375254.8	c.3166-35C>G		intron_variant	Intron 23 of 105	1	NM_020765.3	ENSP00000364403.3
UBR4	ENST00000419533.1	n.814-35C>G		intron_variant	Intron 5 of 29	5

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101469 AN: 151954 Hom.: 34672 Cov.: 32

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.643

GnomAD2 exomes AF: 0.644 AC: 161162 AN: 250062 AF XY: 0.630

Gnomad AFR exome AF: 0.790

Gnomad AMR exome AF: 0.791

Gnomad ASJ exome AF: 0.568

Gnomad EAS exome AF: 0.813

Gnomad FIN exome AF: 0.526

Gnomad NFE exome AF: 0.609

Gnomad OTH exome AF: 0.619

GnomAD4 exome AF: 0.622 AC: 908681 AN: 1460556 Hom.: 285768 Cov.: 57 AF XY: 0.617 AC XY: 448228 AN XY: 726422

African (AFR) AF: 0.795 AC: 26574 AN: 33422

American (AMR) AF: 0.783 AC: 34890 AN: 44580

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 15011 AN: 26092

East Asian (EAS) AF: 0.830 AC: 32920 AN: 39678

South Asian (SAS) AF: 0.547 AC: 47113 AN: 86198

European-Finnish (FIN) AF: 0.536 AC: 28579 AN: 53362

Middle Eastern (MID) AF: 0.494 AC: 2845 AN: 5764

European-Non Finnish (NFE) AF: 0.614 AC: 682763 AN: 1111134

Other (OTH) AF: 0.630 AC: 37986 AN: 60326

GnomAD4 genome AF: 0.668 AC: 101585 AN: 152072 Hom.: 34732 Cov.: 32 AF XY: 0.665 AC XY: 49436 AN XY: 74338

African (AFR) AF: 0.789 AC: 32744 AN: 41500

American (AMR) AF: 0.715 AC: 10922 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2008 AN: 3470

East Asian (EAS) AF: 0.810 AC: 4185 AN: 5168

South Asian (SAS) AF: 0.551 AC: 2654 AN: 4818

European-Finnish (FIN) AF: 0.519 AC: 5484 AN: 10566

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.611 AC: 41502 AN: 67956

Other (OTH) AF: 0.643 AC: 1359 AN: 2112

Alfa AF: 0.629 Hom.: 5610

Bravo AF: 0.693

Asia WGS AF: 0.713 AC: 2479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.0
DANN	Benign	0.52
PhyloP100		-0.60
BranchPoint Hunter		0.0
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

Other links and lift over

dbSNP: rs951908; hg19: chr1-19499835;