2-135765140-A-G

Position:

• chr2-135765140-A-G

Variant summary

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

The NM_014607.4(UBXN4):​c.602+3229A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,066 control chromosomes in the GnomAD database, including 29,515 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 0.60 (29515 hom., cov: 33)
• Consequence: UBXN4 NM_014607.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.534

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBXN4	NM_014607.4	c.602+3229A>G		intron_variant		ENST00000272638.14	NP_055422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBXN4	ENST00000272638.14	c.602+3229A>G		intron_variant		1	NM_014607.4	ENSP00000272638	P1
UBXN4	ENST00000490163.5	n.302-4629A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90515 AN: 151948 Hom.: 29512 Cov.: 33

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.595 AC: 90546 AN: 152066 Hom.: 29515 Cov.: 33 AF XY: 0.585 AC XY: 43504 AN XY: 74318

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.748

Gnomad4 NFE AF: 0.760

Gnomad4 OTH AF: 0.531

Alfa AF: 0.681 Hom.: 49378

Bravo AF: 0.569

Asia WGS AF: 0.441 AC: 1535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.6
DANN	Benign	0.69

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: rs9287442; hg19: chr2-136522710;