rs6430585

Positions:

• chr2-135749357-A-C
• chr2-135749357-A-G
• chr2-135749357-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBXN4	NM_014607.4	c.185+988A>C		intron_variant		ENST00000272638.14	NP_055422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBXN4	ENST00000272638.14	c.185+988A>C		intron_variant		1	NM_014607.4	ENSP00000272638	P1

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

Gnomad4 AFR AF: 0.700

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.781

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.785

Gnomad4 NFE AF: 0.791

Gnomad4 OTH AF: 0.668

Alfa AF: 0.751 Hom.: 43246

Bravo AF: 0.731

Asia WGS AF: 0.740 AC: 2576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.58
DANN	Benign	0.35

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: rs6430585; hg19: chr2-136506927;