dbSNP rs910760: CTNNBL1:c.1604-332A>C (chr20-37871593-A-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_030877.5(CTNNBL1):c.1604-332A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 152,044 control chromosomes in the GnomAD database, including 42,927 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 0.75 ( 42927 hom., cov: 31)

Consequence

CTNNBL1
NM_030877.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.104

Publications

7 publications found

Variant links:

Genes affected

CTNNBL1 (HGNC:15879): (catenin beta like 1) The protein encoded by this gene is a component of the pre-mRNA-processing factor 19-cell division cycle 5-like (PRP19-CDC5L) protein complex, which activates pre-mRNA splicing and is an integral part of the spliceosome. The encoded protein is also a nuclear localization sequence binding protein, and binds to activation-induced deaminase and is important for antibody diversification. This gene may also be associated with the development of obesity. Alternative splicing results in multiple transcript variants. A pseudogene of this gene has been defined on the X chromosome. [provided by RefSeq, Jul 2013]

CTNNBL1 Gene-Disease associations (from GenCC):

common variable immunodeficiency
Inheritance: AR Classification: LIMITED Submitted by: ClinGen
immunodeficiency 99 with hypogammaglobulinemia and autoimmune cytopenias
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

CTNNBL1 links:

ENSG00000305049 (HGNC:):

ENSG00000305049 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=-1.01).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CTNNBL1	NM_030877.5 link	c.1604-332A>C	intron_variant	Intron 15 of 15	ENST00000361383.11	NP_110517.2	Q8WYA6-1
CTNNBL1	NM_001281495.2 link	c.1523-332A>C	intron_variant	Intron 16 of 16		NP_001268424.1	Q8WYA6-4
CTNNBL1	XM_024451947.2 link	c.1523-332A>C	intron_variant	Intron 16 of 16		XP_024307715.1
CTNNBL1	XM_011528917.3 link	c.1274-332A>C	intron_variant	Intron 13 of 13		XP_011527219.1	Q8WYA6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNBL1	ENST00000361383.11 link	c.1604-332A>C		intron_variant	Intron 15 of 15	1	NM_030877.5	ENSP00000355050.6		Q8WYA6-1
CTNNBL1	ENST00000628103.2 link	c.1523-332A>C		intron_variant	Intron 16 of 16	2		ENSP00000487198.1		Q8WYA6-4

Frequencies

GnomAD3 genomes

AF:

0.750

AC:

113949

AN:

151926

Hom.:

42888

Cov.:

show subpopulations

Gnomad AFR

AF:

0.735

Gnomad AMI

AF:

0.627

Gnomad AMR

AF:

0.820

Gnomad ASJ

AF:

0.868

Gnomad EAS

AF:

0.854

Gnomad SAS

AF:

0.836

Gnomad FIN

AF:

0.652

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.739

Gnomad OTH

AF:

0.779

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.750

AC:

114040

AN:

152044

Hom.:

42927

Cov.:

AF XY:

0.749

AC XY:

55710

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.735

AC:

30467

AN:

41440

American (AMR)

AF:

0.821

AC:

12547

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.868

AC:

3012

AN:

3472

East Asian (EAS)

AF:

0.854

AC:

4420

AN:

5174

South Asian (SAS)

AF:

0.835

AC:

4025

AN:

4818

European-Finnish (FIN)

AF:

0.652

AC:

6894

AN:

10580

Middle Eastern (MID)

AF:

0.823

AC:

242

AN:

294

European-Non Finnish (NFE)

AF:

0.739

AC:

50218

AN:

67962

Other (OTH)

AF:

0.781

AC:

1647

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1453

2906

4360

5813

7266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

862

1724

2586

3448

4310

<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:

0.733

Hom.:

5292

Bravo

AF:

0.762

Asia WGS

AF:

0.839

AC:

2917

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.7

(source)

DANN

Benign

0.39

PhyloP100

-0.10

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over