rs1050115

Positions:

• chr2-135754247-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_014607.4(UBXN4):​c.303A>G​(p.Glu101Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,612,732 control chromosomes in the GnomAD database, including 22,459 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 0.17 (2548 hom., cov: 32)
  • Exomes 𝑓: 0.15 (19911 hom.)
• Consequence: UBXN4 NM_014607.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.859

Genes affected

UBXN4 (HGNC:14860): (UBX domain protein 4) UBXD2 is an integral membrane protein of the endoplasmic reticulum (ER) that binds valosin-containing protein (VCP; MIM 601023) and promotes ER-associated protein degradation (ERAD) (Liang et al., 2006 [PubMed 16968747]).[supplied by OMIM, Mar 2008]

UBXN4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=0.859 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBXN4	NM_014607.4	c.303A>G	p.Glu101Glu	synonymous_variant	4/13	ENST00000272638.14	NP_055422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBXN4	ENST00000272638.14	c.303A>G	p.Glu101Glu	synonymous_variant	4/13	1	NM_014607.4	ENSP00000272638.9

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26008 AN: 152044 Hom.: 2549 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.240

GnomAD3 exomes AF: 0.185 AC: 46235 AN: 249322 Hom.: 5344 AF XY: 0.191 AC XY: 25854 AN XY: 135278

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.185

Gnomad ASJ exome AF: 0.441

Gnomad EAS exome AF: 0.179

Gnomad SAS exome AF: 0.225

Gnomad FIN exome AF: 0.135

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.227

GnomAD4 exome AF: 0.147 AC: 214712 AN: 1460570 Hom.: 19911 Cov.: 31 AF XY: 0.153 AC XY: 110857 AN XY: 726638

Gnomad4 AFR exome AF: 0.151

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.434

Gnomad4 EAS exome AF: 0.153

Gnomad4 SAS exome AF: 0.222

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.130

Gnomad4 OTH exome AF: 0.180

GnomAD4 genome AF: 0.171 AC: 26022 AN: 152162 Hom.: 2548 Cov.: 32 AF XY: 0.173 AC XY: 12906 AN XY: 74392

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.244

Alfa AF: 0.193 Hom.: 5066

Bravo AF: 0.175

Asia WGS AF: 0.183 AC: 636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	9.4
DANN	Benign	0.60
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1050115; hg19: chr2-136511817; COSMIC: COSV55633547; COSMIC: COSV55633547;