dbSNP rs1050115: UBXN4:p.Glu101Glu (chr2-135754247-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_014607.4(UBXN4):c.303A>G(p.Glu101Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,612,732 control chromosomes in the GnomAD database, including 22,459 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.17 ( 2548 hom., cov: 32)

Exomes 𝑓: 0.15 ( 19911 hom. )

Consequence

UBXN4
NM_014607.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.859

Publications

29 publications found

Variant links:

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]

UBXN4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 2-135754247-A-G is Benign according to our data. Variant chr2-135754247-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 4076127.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.859 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBXN4	NM_014607.4 link	c.303A>G	p.Glu101Glu	synonymous_variant	Exon 4 of 13	ENST00000272638.14	NP_055422.1	Q92575

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBXN4	ENST00000272638.14 link	c.303A>G	p.Glu101Glu	synonymous_variant	Exon 4 of 13	1	NM_014607.4	ENSP00000272638.9		Q92575

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

26008

AN:

152044

Hom.:

2549

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.232

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:

0.240

GnomAD2 exomes

AF:

0.185

AC:

46235

AN:

249322

AF XY:

0.191

show subpopulations

Gnomad AFR exome

AF:

0.141

Gnomad AMR exome

AF:

0.185

Gnomad ASJ exome

AF:

0.441

Gnomad EAS exome

AF:

0.179

Gnomad FIN exome

AF:

0.135

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.227

GnomAD4 exome

AF:

0.147

AC:

214712

AN:

1460570

Hom.:

19911

Cov.:

AF XY:

0.153

AC XY:

110857

AN XY:

726638

show subpopulations

African (AFR)

AF:

0.151

AC:

5057

AN:

33458

American (AMR)

AF:

0.189

AC:

8465

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.434

AC:

11309

AN:

26086

East Asian (EAS)

AF:

0.153

AC:

6058

AN:

39676

South Asian (SAS)

AF:

0.222

AC:

19173

AN:

86192

European-Finnish (FIN)

AF:

0.136

AC:

7287

AN:

53412

Middle Eastern (MID)

AF:

0.360

AC:

2074

AN:

5758

European-Non Finnish (NFE)

AF:

0.130

AC:

144430

AN:

1110968

Other (OTH)

AF:

0.180

AC:

10859

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

8207

16414

24622

32829

41036

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4814

9628

14442

19256

24070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.171

AC:

26022

AN:

152162

Hom.:

2548

Cov.:

AF XY:

0.173

AC XY:

12906

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.142

AC:

5877

AN:

41498

American (AMR)

AF:

0.232

AC:

3549

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.442

AC:

1535

AN:

3470

East Asian (EAS)

AF:

0.180

AC:

934

AN:

5184

South Asian (SAS)

AF:

0.219

AC:

1054

AN:

4818

European-Finnish (FIN)

AF:

0.131

AC:

1390

AN:

10592

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.160

AC:

10913

AN:

68002

Other (OTH)

AF:

0.244

AC:

515

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1085

2169

3254

4338

5423

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

280

560

840

1120

1400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.189

Hom.:

6034

Bravo

AF:

0.175

Asia WGS

AF:

0.183

AC:

636

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

9.4

(source)

DANN

Benign

0.60

PhyloP100

0.86

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over