rs10188066

Positions:

• chr2-135781943-G-A
• chr2-135781943-G-C

Variant summary

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

The NM_014607.4(UBXN4):​c.1389-806G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 152,032 control chromosomes in the GnomAD database, including 30,366 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 0.61 (30366 hom., cov: 31)
• Consequence: UBXN4 NM_014607.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBXN4	NM_014607.4	c.1389-806G>A		intron_variant		ENST00000272638.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBXN4	ENST00000272638.14	c.1389-806G>A		intron_variant		1	NM_014607.4	P1
UBXN4	ENST00000490163.5	n.1088-806G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92186 AN: 151914 Hom.: 30365 Cov.: 31

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.607 AC: 92217 AN: 152032 Hom.: 30366 Cov.: 31 AF XY: 0.598 AC XY: 44451 AN XY: 74316

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.628

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.747

Gnomad4 NFE AF: 0.761

Gnomad4 OTH AF: 0.542

Alfa AF: 0.686 Hom.: 51315

Bravo AF: 0.584

Asia WGS AF: 0.514 AC: 1790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.56
DANN	Benign	0.29

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: rs10188066; hg19: chr2-136539513;