rs1469996

Variant names:

• chr2-135784990-A-G
• rs1469996
• NM_014607.4:c.*2103A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_014607.4(UBXN4):​c.*2103A>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 0.215 in 152,174 control chromosomes in the GnomAD database, including 4,010 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 0.22 (4008 hom., cov: 31)
  • Exomes 𝑓: 0.21 (2 hom.)
• Consequence: UBXN4 NM_014607.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.90
• Publications: 14 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBXN4	NM_014607.4	c.*2103A>G		3_prime_UTR_variant	Exon 13 of 13	ENST00000272638.14	NP_055422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBXN4	ENST00000272638.14	c.*2103A>G		3_prime_UTR_variant	Exon 13 of 13	1	NM_014607.4	ENSP00000272638.9
UBXN4	ENST00000490163.5	n.3329A>G		non_coding_transcript_exon_variant	Exon 9 of 9	2

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32732 AN: 151970 Hom.: 4007 Cov.: 31

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.297

GnomAD4 exome AF: 0.209 AC: 18 AN: 86 Hom.: 2 Cov.: 0 AF XY: 0.224 AC XY: 13 AN XY: 58

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.214 AC: 18 AN: 84

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.215 AC: 32757 AN: 152088 Hom.: 4008 Cov.: 31 AF XY: 0.221 AC XY: 16414 AN XY: 74328

African (AFR) AF: 0.155 AC: 6450 AN: 41526

American (AMR) AF: 0.322 AC: 4914 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1675 AN: 3462

East Asian (EAS) AF: 0.201 AC: 1041 AN: 5174

South Asian (SAS) AF: 0.278 AC: 1339 AN: 4822

European-Finnish (FIN) AF: 0.213 AC: 2251 AN: 10564

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.208 AC: 14135 AN: 67958

Other (OTH) AF: 0.300 AC: 632 AN: 2108

Alfa AF: 0.221 Hom.: 2545

Bravo AF: 0.219

Asia WGS AF: 0.219 AC: 762 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	14
DANN	Benign	0.88
PhyloP100		2.9
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: rs1469996; hg19: chr2-136542560;