chr20-37857818-G-C

Variant names:

• chr20-37857818-G-C
• rs4811233
• NM_030877.5:c.1393-2081G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030877.5(CTNNBL1):​c.1393-2081G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 152,158 control chromosomes in the GnomAD database, including 39,323 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 0.72 (39323 hom., cov: 32)
• Consequence: CTNNBL1 NM_030877.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220
• Publications: 1 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

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.1393-2081G>C		intron	N/A	NP_110517.2
	CTNNBL1	NM_001281495.2		c.1312-2081G>C		intron	N/A	NP_001268424.1	Q8WYA6-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNBL1	ENST00000361383.11	TSL:1 MANE Select	c.1393-2081G>C		intron	N/A	ENSP00000355050.6	Q8WYA6-1
	CTNNBL1	ENST00000628103.2	TSL:2	c.1312-2081G>C		intron	N/A	ENSP00000487198.1	Q8WYA6-4
	CTNNBL1	ENST00000373473.5	TSL:1	c.832-2081G>C		intron	N/A	ENSP00000362572.1	Q8WYA6-2

Frequencies

GnomAD3 genomes AF: 0.717 AC: 108969 AN: 152040 Hom.: 39278 Cov.: 32

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.741

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

GnomAD4 genome AF: 0.717 AC: 109070 AN: 152158 Hom.: 39323 Cov.: 32 AF XY: 0.715 AC XY: 53204 AN XY: 74376

African (AFR) AF: 0.769 AC: 31931 AN: 41512

American (AMR) AF: 0.791 AC: 12090 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.787 AC: 2731 AN: 3472

East Asian (EAS) AF: 0.826 AC: 4278 AN: 5178

South Asian (SAS) AF: 0.750 AC: 3619 AN: 4824

European-Finnish (FIN) AF: 0.585 AC: 6195 AN: 10582

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45917 AN: 67982

Other (OTH) AF: 0.744 AC: 1572 AN: 2112

Alfa AF: 0.544 Hom.: 905

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.3
DANN	Benign	0.51
PhyloP100		-0.022
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4811233; hg19: chr20-36486220;