chr2-135770464-C-A

Variant names:

• chr2-135770464-C-A
• rs2304601
• NM_014607.4:c.658-107C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.87).
• 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 rank	MANE	Protein	UniProt
UBXN4	NM_014607.4	c.658-107C>A		intron_variant	Intron 7 of 12	ENST00000272638.14	NP_055422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBXN4	ENST00000272638.14	c.658-107C>A		intron_variant	Intron 7 of 12	1	NM_014607.4	ENSP00000272638.9
UBXN4	ENST00000490163.5	n.357-107C>A		intron_variant	Intron 3 of 8	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

African (AFR) AF: 0.154 AC: 2078 AN: 13536

American (AMR) AF: 0.207 AC: 2391 AN: 11540

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 5761 AN: 13180

East Asian (EAS) AF: 0.145 AC: 4009 AN: 27612

South Asian (SAS) AF: 0.219 AC: 7588 AN: 34598

European-Finnish (FIN) AF: 0.133 AC: 5434 AN: 40770

Middle Eastern (MID) AF: 0.411 AC: 882 AN: 2144

European-Non Finnish (NFE) AF: 0.145 AC: 61030 AN: 421774

Other (OTH) AF: 0.194 AC: 5586 AN: 28832

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

African (AFR) AF: 0.143 AC: 5924 AN: 41540

American (AMR) AF: 0.230 AC: 3519 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1536 AN: 3472

East Asian (EAS) AF: 0.180 AC: 934 AN: 5178

South Asian (SAS) AF: 0.219 AC: 1056 AN: 4818

European-Finnish (FIN) AF: 0.131 AC: 1381 AN: 10572

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10871 AN: 68014

Other (OTH) AF: 0.242 AC: 513 AN: 2116

Alfa AF: 0.169 Hom.: 328

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
PhyloP100		-3.2
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: rs2304601; hg19: chr2-136528034;