rs3213889

Variant names:

• chr2-135754005-A-G
• rs3213889
• NM_014607.4:c.215-154A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014607.4(UBXN4):​c.215-154A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 594,288 control chromosomes in the GnomAD database, including 123,210 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 0.53 (25501 hom., cov: 33)
  • Exomes 𝑓: 0.64 (97709 hom.)
• Consequence: UBXN4 NM_014607.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBXN4	NM_014607.4	c.215-154A>G		intron_variant	Intron 3 of 12	ENST00000272638.14	NP_055422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBXN4	ENST00000272638.14	c.215-154A>G		intron_variant	Intron 3 of 12	1	NM_014607.4	ENSP00000272638.9

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80277 AN: 152050 Hom.: 25499 Cov.: 33

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.482

GnomAD4 exome AF: 0.639 AC: 282591 AN: 442120 Hom.: 97709 Cov.: 5 AF XY: 0.627 AC XY: 146793 AN XY: 234276

African (AFR) AF: 0.212 AC: 2366 AN: 11186

American (AMR) AF: 0.474 AC: 7530 AN: 15870

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 4915 AN: 13078

East Asian (EAS) AF: 0.430 AC: 12234 AN: 28454

South Asian (SAS) AF: 0.431 AC: 17499 AN: 40646

European-Finnish (FIN) AF: 0.731 AC: 26538 AN: 36290

Middle Eastern (MID) AF: 0.291 AC: 599 AN: 2056

European-Non Finnish (NFE) AF: 0.727 AC: 195945 AN: 269598

Other (OTH) AF: 0.600 AC: 14965 AN: 24942

GnomAD4 genome AF: 0.528 AC: 80280 AN: 152168 Hom.: 25501 Cov.: 33 AF XY: 0.519 AC XY: 38587 AN XY: 74394

African (AFR) AF: 0.220 AC: 9133 AN: 41520

American (AMR) AF: 0.438 AC: 6700 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1288 AN: 3472

East Asian (EAS) AF: 0.381 AC: 1972 AN: 5180

South Asian (SAS) AF: 0.386 AC: 1861 AN: 4820

European-Finnish (FIN) AF: 0.732 AC: 7752 AN: 10586

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.732 AC: 49772 AN: 67990

Other (OTH) AF: 0.478 AC: 1009 AN: 2112

Alfa AF: 0.593 Hom.: 9209

Bravo AF: 0.496

Asia WGS AF: 0.393 AC: 1367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.51
PhyloP100		0.14
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: rs3213889; hg19: chr2-136511575; COSMIC: COSV55636189; COSMIC: COSV55636189;