dbSNP rs11592567: ENSG00000230534:n.118G>A (chr10-35120441-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000450742.5(ENSG00000230534):n.118G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,976 control chromosomes in the GnomAD database, including 7,057 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 0.29 ( 7057 hom., cov: 32)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

ENSG00000230534
ENST00000450742.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.31

Publications

9 publications found

Variant links:

Genes affected

ENSG00000230534 (HGNC:):

ENSG00000230534 links:

CUL2 (HGNC:2552): (cullin 2) Enables ubiquitin protein ligase binding activity. Predicted to be involved in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process and protein ubiquitination. Predicted to act upstream of or within protein catabolic process. Located in nucleoplasm. Part of Cul2-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

CUL2 links:

Genome browser will be placed here

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=-0.86).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
CUL2	XM_011519743.1 link	c.-81G>A	5_prime_UTR_variant	Exon 2 of 23	XP_011518045.1
CUL2	XM_047425852.1 link	c.-81G>A	5_prime_UTR_variant	Exon 2 of 23	XP_047281808.1
CUL2	XM_011519744.1 link	c.-51+6164G>A	intron_variant	Intron 1 of 21	XP_011518046.1
CUL2	XM_011519745.2 link	c.-51+6375G>A	intron_variant	Intron 1 of 21	XP_011518047.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ENSG00000230534	ENST00000450742.5 link	n.118G>A	non_coding_transcript_exon_variant	Exon 2 of 5	5
ENSG00000230534	ENST00000457255.1 link	n.270G>A	non_coding_transcript_exon_variant	Exon 2 of 4	5
CUL2	ENST00000688736.1 link	c.-81G>A	5_prime_UTR_variant	Exon 2 of 7		ENSP00000510643.1	A0A8I5KWB8

Frequencies

GnomAD3 genomes

AF:

0.293

AC:

44479

AN:

151856

Hom.:

7045

Cov.:

show subpopulations

Gnomad AFR

AF:

0.162

Gnomad AMI

AF:

0.257

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.399

Gnomad EAS

AF:

0.296

Gnomad SAS

AF:

0.348

Gnomad FIN

AF:

0.390

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.346

Gnomad OTH

AF:

0.316

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.293

AC:

44524

AN:

151974

Hom.:

7057

Cov.:

AF XY:

0.295

AC XY:

21949

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.162

AC:

6718

AN:

41458

American (AMR)

AF:

0.299

AC:

4562

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.399

AC:

1382

AN:

3466

East Asian (EAS)

AF:

0.296

AC:

1529

AN:

5166

South Asian (SAS)

AF:

0.349

AC:

1681

AN:

4816

European-Finnish (FIN)

AF:

0.390

AC:

4108

AN:

10532

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.346

AC:

23541

AN:

67960

Other (OTH)

AF:

0.323

AC:

681

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1612

3224

4836

6448

8060

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

456

912

1368

1824

2280

<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:

0.302

Hom.:

973

Bravo

AF:

0.279

Asia WGS

AF:

0.344

AC:

1195

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.5

(source)

DANN

Benign

0.68

PhyloP100

-1.3

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over