NM_014607.4:c.185+988A>C

Variant names:

• chr2-135749357-A-C
• rs6430585
• NM_014607.4:c.185+988A>C

Variant summary

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

The NM_014607.4(UBXN4):​c.185+988A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 152,108 control chromosomes in the GnomAD database, including 42,156 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 0.74 (42156 hom., cov: 32)
• Consequence: UBXN4 NM_014607.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.713
• Publications: 27 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014607.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBXN4	NM_014607.4	MANE Select	c.185+988A>C		intron	N/A	NP_055422.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBXN4	ENST00000272638.14	TSL:1 MANE Select	c.185+988A>C		intron	N/A	ENSP00000272638.9
	UBXN4	ENST00000415164.5	TSL:4	c.293+988A>C		intron	N/A	ENSP00000401748.1
	UBXN4	ENST00000416538.5	TSL:5	n.185+988A>C		intron	N/A	ENSP00000391586.1

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112518 AN: 151990 Hom.: 42128 Cov.: 32

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.740 AC: 112603 AN: 152108 Hom.: 42156 Cov.: 32 AF XY: 0.735 AC XY: 54635 AN XY: 74352

African (AFR) AF: 0.700 AC: 29033 AN: 41476

American (AMR) AF: 0.658 AC: 10054 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 1757 AN: 3470

East Asian (EAS) AF: 0.781 AC: 4049 AN: 5184

South Asian (SAS) AF: 0.689 AC: 3327 AN: 4828

European-Finnish (FIN) AF: 0.785 AC: 8295 AN: 10562

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.791 AC: 53795 AN: 67994

Other (OTH) AF: 0.668 AC: 1411 AN: 2112

Alfa AF: 0.750 Hom.: 79315

Bravo AF: 0.731

Asia WGS AF: 0.740 AC: 2576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.58
DANN	Benign	0.35
PhyloP100		-0.71
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: rs6430585; hg19: chr2-136506927;