rs6021428

Variant names:

• chr20-37862631-C-T
• rs6021428
• NM_030877.5:c.1603+2287C>T

Variant summary

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

The ENST00000361383.11(CTNNBL1):​c.1603+2287C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0666 in 152,196 control chromosomes in the GnomAD database, including 424 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 0.067 (424 hom., cov: 31)
• Consequence: CTNNBL1 ENST00000361383.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.50
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0829 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361383.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNBL1	NM_030877.5	MANE Select	c.1603+2287C>T		intron	N/A	NP_110517.2
	CTNNBL1	NM_001281495.2		c.1522+2287C>T		intron	N/A	NP_001268424.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNBL1	ENST00000361383.11	TSL:1 MANE Select	c.1603+2287C>T		intron	N/A	ENSP00000355050.6
	CTNNBL1	ENST00000628103.2	TSL:2	c.1522+2287C>T		intron	N/A	ENSP00000487198.1
	CTNNBL1	ENST00000373473.5	TSL:1	c.1042+2287C>T		intron	N/A	ENSP00000362572.1

Frequencies

GnomAD3 genomes AF: 0.0664 AC: 10104 AN: 152078 Hom.: 420 Cov.: 31

Gnomad AFR AF: 0.0848

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.0528

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.00945

Gnomad SAS AF: 0.0298

Gnomad FIN AF: 0.0732

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0634

Gnomad OTH AF: 0.0665

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

GnomAD4 genome AF: 0.0666 AC: 10129 AN: 152196 Hom.: 424 Cov.: 31 AF XY: 0.0657 AC XY: 4886 AN XY: 74420

African (AFR) AF: 0.0853 AC: 3539 AN: 41508

American (AMR) AF: 0.0528 AC: 807 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3470

East Asian (EAS) AF: 0.00947 AC: 49 AN: 5174

South Asian (SAS) AF: 0.0298 AC: 144 AN: 4830

European-Finnish (FIN) AF: 0.0732 AC: 775 AN: 10588

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0634 AC: 4312 AN: 68010

Other (OTH) AF: 0.0653 AC: 138 AN: 2112

Alfa AF: 0.0692 Hom.: 44

Bravo AF: 0.0658

Asia WGS AF: 0.0320 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.17
DANN	Benign	0.55
PhyloP100		-3.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs6021428; hg19: chr20-36491033;