rs186475150

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_030877.5(CTNNBL1):c.733C>G(p.Leu245Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000468 in 1,613,942 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 2 hom. )

Consequence

CTNNBL1
NM_030877.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.986

Publications

4 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01103279).

BP6

Variant 20-37768027-C-G is Benign according to our data. Variant chr20-37768027-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 725816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030877.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNBL1	NM_030877.5	MANE Select	c.733C>G	p.Leu245Val	missense	Exon 7 of 16	NP_110517.2
	CTNNBL1	NM_001281495.2		c.652C>G	p.Leu218Val	missense	Exon 8 of 17	NP_001268424.1	Q8WYA6-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTNNBL1	ENST00000361383.11	TSL:1 MANE Select	c.733C>G	p.Leu245Val	missense	Exon 7 of 16	ENSP00000355050.6	Q8WYA6-1
CTNNBL1	ENST00000628103.2	TSL:2	c.652C>G	p.Leu218Val	missense	Exon 8 of 17	ENSP00000487198.1	Q8WYA6-4
CTNNBL1	ENST00000373473.5	TSL:1	c.172C>G	p.Leu58Val	missense	Exon 4 of 13	ENSP00000362572.1	Q8WYA6-2

Frequencies

GnomAD3 genomes

AF:

0.00215

AC:

327

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00730

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000983

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.000744

AC:

187

AN:

251298

AF XY:

0.000508

show subpopulations

Gnomad AFR exome

AF:

0.00941

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000293

AC:

428

AN:

1461730

Hom.:

Cov.:

AF XY:

0.000245

AC XY:

178

AN XY:

727174

show subpopulations

African (AFR)

AF:

0.00869

AC:

291

AN:

33470

American (AMR)

AF:

0.000648

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000468

AC:

AN:

1111912

Other (OTH)

AF:

0.000745

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00215

AC:

327

AN:

152212

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

149

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.00727

AC:

302

AN:

41516

American (AMR)

AF:

0.000982

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000208

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68022

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000608

Hom.:

Bravo

AF:

0.00283

ExAC

AF:

0.000832

AC:

101

ClinVar

ClinVar submissions as Germline

Significance:Likely 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

0.21

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.45

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.49

MutationAssessor

Pathogenic

3.0

PhyloP100

0.99

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.47

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.014

Polyphen

0.98

Vest4

0.63

MVP

0.55

MPC

0.57

ClinPred

0.058

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.61

gMVP

0.78

Mutation Taster

=69/31

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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