chr1-156041653-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020131.5(UBQLN4):c.1485A>G(p.Ile495Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 1,565,318 control chromosomes in the GnomAD database, including 280,130 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I495V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.54 ( 23397 hom., cov: 33)

Exomes 𝑓: 0.60 ( 256733 hom. )

Consequence

UBQLN4
NM_020131.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.716

Publications

42 publications found

Variant links:

Genes affected

UBQLN4 (HGNC:1237): (ubiquilin 4) Enables K48-linked polyubiquitin modification-dependent protein binding activity and identical protein binding activity. Involved in cellular response to DNA damage stimulus; negative regulation of double-strand break repair via homologous recombination; and regulation of cellular catabolic process. Located in several cellular components, including autophagosome; nucleoplasm; and site of DNA damage. Part of protein-containing complex. Colocalizes with cytosolic proteasome complex and nuclear proteasome complex. [provided by Alliance of Genome Resources, Apr 2022]

UBQLN4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.676082E-6).

BP6

Variant 1-156041653-T-C is Benign according to our data. Variant chr1-156041653-T-C is described in ClinVar as Benign. ClinVar VariationId is 674310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020131.5. 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
	UBQLN4	NM_020131.5	MANE Select	c.1485A>G	p.Ile495Met	missense	Exon 10 of 11	NP_064516.2
	UBQLN4	NM_001304342.2		c.1425A>G	p.Ile475Met	missense	Exon 10 of 11	NP_001291271.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
UBQLN4	ENST00000368309.4	TSL:1 MANE Select	c.1485A>G	p.Ile495Met	missense	Exon 10 of 11	ENSP00000357292.3
UBQLN4	ENST00000879792.1		c.1485A>G	p.Ile495Met	missense	Exon 10 of 11	ENSP00000549851.1
UBQLN4	ENST00000932515.1		c.1479A>G	p.Ile493Met	missense	Exon 10 of 11	ENSP00000602574.1

Frequencies

GnomAD3 genomes

AF:

0.542

AC:

82370

AN:

151898

Hom.:

23377

Cov.:

show subpopulations

Gnomad AFR

AF:

0.439

Gnomad AMI

AF:

0.552

Gnomad AMR

AF:

0.549

Gnomad ASJ

AF:

0.586

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.537

Gnomad FIN

AF:

0.601

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.622

Gnomad OTH

AF:

0.551

GnomAD2 exomes

AF:

0.529

AC:

100560

AN:

189974

AF XY:

0.537

show subpopulations

Gnomad AFR exome

AF:

0.432

Gnomad AMR exome

AF:

0.451

Gnomad ASJ exome

AF:

0.578

Gnomad EAS exome

AF:

0.127

Gnomad FIN exome

AF:

0.594

Gnomad NFE exome

AF:

0.618

Gnomad OTH exome

AF:

0.559

GnomAD4 exome

AF:

0.596

AC:

841922

AN:

1413302

Hom.:

256733

Cov.:

AF XY:

0.595

AC XY:

415849

AN XY:

699304

show subpopulations

African (AFR)

AF:

0.429

AC:

13766

AN:

32104

American (AMR)

AF:

0.462

AC:

16380

AN:

35476

Ashkenazi Jewish (ASJ)

AF:

0.588

AC:

14176

AN:

24106

East Asian (EAS)

AF:

0.151

AC:

5819

AN:

38418

South Asian (SAS)

AF:

0.529

AC:

42518

AN:

80340

European-Finnish (FIN)

AF:

0.607

AC:

31329

AN:

51582

Middle Eastern (MID)

AF:

0.592

AC:

3313

AN:

5598

European-Non Finnish (NFE)

AF:

0.626

AC:

680973

AN:

1087324

Other (OTH)

AF:

0.577

AC:

33648

AN:

58354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

17152

34304

51455

68607

85759

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18198

36396

54594

72792

90990

<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:

0.542

AC:

82419

AN:

152016

Hom.:

23397

Cov.:

AF XY:

0.539

AC XY:

40032

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.439

AC:

18191

AN:

41422

American (AMR)

AF:

0.548

AC:

8375

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.586

AC:

2035

AN:

3470

East Asian (EAS)

AF:

0.145

AC:

752

AN:

5176

South Asian (SAS)

AF:

0.537

AC:

2584

AN:

4816

European-Finnish (FIN)

AF:

0.601

AC:

6361

AN:

10584

Middle Eastern (MID)

AF:

0.592

AC:

174

AN:

294

European-Non Finnish (NFE)

AF:

0.622

AC:

42281

AN:

67954

Other (OTH)

AF:

0.552

AC:

1164

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1876

3752

5629

7505

9381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

710

1420

2130

2840

3550

<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:

0.588

Hom.:

100399

Bravo

AF:

0.530

TwinsUK

AF:

0.626

AC:

2323

ALSPAC

AF:

0.629

AC:

2424

ESP6500AA

AF:

0.436

AC:

1918

ESP6500EA

AF:

0.613

AC:

5274

ExAC

AF:

0.512

AC:

61077

Asia WGS

AF:

0.373

AC:

1295

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.0090

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.052

MetaRNN

Benign

0.0000057

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.72

PrimateAI

Benign

0.40

PROVEAN

Benign

0.13

REVEL

Benign

0.029

Sift

Benign

0.42

Sift4G

Benign

0.27

Polyphen

0.0070

Vest4

0.021

MPC

0.67

ClinPred

0.0014

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.051

gMVP

0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over