Genetic Variant UBQLN4:c.*756A>G (chr1-156036222-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020131.5(UBQLN4):c.*756A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 985,378 control chromosomes in the GnomAD database, including 36,136 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 0.27 ( 6733 hom., cov: 31)

Exomes 𝑓: 0.26 ( 29403 hom. )

Consequence

UBQLN4
NM_020131.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.502

Publications

6 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
UBQLN4	NM_020131.5 link	c.*756A>G	3_prime_UTR_variant	Exon 11 of 11	ENST00000368309.4	NP_064516.2	Q9NRR5-1
UBQLN4	NM_001304342.2 link	c.*756A>G	3_prime_UTR_variant	Exon 11 of 11		NP_001291271.1	Q9NRR5Q59F94B4DZF6
UBQLN4	XM_047425666.1 link	c.*756A>G	3_prime_UTR_variant	Exon 11 of 11		XP_047281622.1
UBQLN4	XM_024448469.2 link	c.1654-2946A>G	intron_variant	Intron 10 of 10		XP_024304237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBQLN4	ENST00000368309.4 link	c.*756A>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_020131.5	ENSP00000357292.3		Q9NRR5-1

Frequencies

GnomAD3 genomes

AF:

0.269

AC:

40909

AN:

151990

Hom.:

6726

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.330

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.834

Gnomad SAS

AF:

0.301

Gnomad FIN

AF:

0.295

Gnomad MID

AF:

0.156

Gnomad NFE

AF:

0.261

Gnomad OTH

AF:

0.274

GnomAD4 exome

AF:

0.263

AC:

218902

AN:

833270

Hom.:

29403

Cov.:

AF XY:

0.262

AC XY:

100705

AN XY:

384806

show subpopulations

African (AFR)

AF:

0.182

AC:

2876

AN:

15786

American (AMR)

AF:

0.367

AC:

361

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

1114

AN:

5152

East Asian (EAS)

AF:

0.818

AC:

3082

AN:

3768

South Asian (SAS)

AF:

0.289

AC:

4759

AN:

16460

European-Finnish (FIN)

AF:

0.318

AC:

AN:

280

Middle Eastern (MID)

AF:

0.185

AC:

300

AN:

1620

European-Non Finnish (NFE)

AF:

0.261

AC:

198504

AN:

761920

Other (OTH)

AF:

0.286

AC:

7817

AN:

27300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

10653

21306

31958

42611

53264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.269

AC:

40934

AN:

152108

Hom.:

6733

Cov.:

AF XY:

0.276

AC XY:

20508

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.188

AC:

7785

AN:

41514

American (AMR)

AF:

0.331

AC:

5052

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

706

AN:

3466

East Asian (EAS)

AF:

0.835

AC:

4328

AN:

5184

South Asian (SAS)

AF:

0.302

AC:

1454

AN:

4820

European-Finnish (FIN)

AF:

0.295

AC:

3124

AN:

10580

Middle Eastern (MID)

AF:

0.161

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.261

AC:

17730

AN:

67978

Other (OTH)

AF:

0.272

AC:

574

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1452

2903

4355

5806

7258

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.255

Hom.:

673

Bravo

AF:

0.275

Asia WGS

AF:

0.515

AC:

1790

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.5

(source)

DANN

Benign

0.69

PhyloP100

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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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1-156036222-T-C

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