20-37843383-T-C

Variant names:

• chr20-37843383-T-C
• rs2179320
• NM_030877.5:c.1392+964T>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.1392+964T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 152,176 control chromosomes in the GnomAD database, including 50,195 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 0.81 (50195 hom., cov: 32)
• Consequence: CTNNBL1 NM_030877.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.858 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.1392+964T>C		intron	N/A	NP_110517.2
	CTNNBL1	NM_001281495.2		c.1311+964T>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.1392+964T>C		intron	N/A	ENSP00000355050.6	Q8WYA6-1
	CTNNBL1	ENST00000628103.2	TSL:2	c.1311+964T>C		intron	N/A	ENSP00000487198.1	Q8WYA6-4
	CTNNBL1	ENST00000373473.5	TSL:1	c.831+964T>C		intron	N/A	ENSP00000362572.1	Q8WYA6-2

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123443 AN: 152058 Hom.: 50153 Cov.: 32

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.894

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.891

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.794

Gnomad OTH AF: 0.844

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

GnomAD4 genome AF: 0.812 AC: 123539 AN: 152176 Hom.: 50195 Cov.: 32 AF XY: 0.810 AC XY: 60264 AN XY: 74382

African (AFR) AF: 0.818 AC: 33940 AN: 41500

American (AMR) AF: 0.870 AC: 13311 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.891 AC: 3093 AN: 3472

East Asian (EAS) AF: 0.865 AC: 4482 AN: 5184

South Asian (SAS) AF: 0.864 AC: 4157 AN: 4814

European-Finnish (FIN) AF: 0.724 AC: 7657 AN: 10570

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.794 AC: 54031 AN: 68014

Other (OTH) AF: 0.846 AC: 1790 AN: 2116

Alfa AF: 0.806 Hom.: 9524

Bravo AF: 0.823

Asia WGS AF: 0.871 AC: 3026 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.29
PhyloP100		-0.53
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: rs2179320; hg19: chr20-36471785;