rs2304601

chr2-135770464-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014607.4(UBXN4):c.658-107C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 746,180 control chromosomes in the GnomAD database, including 11,743 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 (2538 hom., cov: 32)
  • Exomes 𝑓: 0.16 (9205 hom.)
• Consequence: UBXN4 NM_014607.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.16

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBXN4	NM_014607.4	c.658-107C>A		intron_variant		ENST00000272638.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBXN4	ENST00000272638.14	c.658-107C>A		intron_variant		1	NM_014607.4	P1
UBXN4	ENST00000490163.5	n.357-107C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25975 AN: 152076 Hom.: 2539 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.230

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: 0.239

GnomAD4 exome AF: 0.160 AC: 94759 AN: 593986 Hom.: 9205 AF XY: 0.164 AC XY: 49485 AN XY: 302268

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.207

Gnomad4 ASJ exome AF: 0.437

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.219

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.145

Gnomad4 OTH exome AF: 0.194

GnomAD4 genome AF: 0.171 AC: 25989 AN: 152194 Hom.: 2538 Cov.: 32 AF XY: 0.173 AC XY: 12883 AN XY: 74380

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.230

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: 0.242

Alfa AF: 0.170 Hom.: 321

Bravo AF: 0.175

Asia WGS AF: 0.182 AC: 634 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.020
Dann	Benign	0.60

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: rs2304601; hg19: chr2-136528034;