chr20-37741864-A-G

Variant names:

• chr20-37741864-A-G
• rs2344481
• NM_030877.5:c.326+4380A>G

Variant summary

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

The NM_030877.5(CTNNBL1):​c.326+4380A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 151,970 control chromosomes in the GnomAD database, including 3,450 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 0.16 (3450 hom., cov: 32)
• Consequence: CTNNBL1 NM_030877.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.381 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNBL1	NM_030877.5	MANE Select	c.326+4380A>G		intron	N/A	NP_110517.2
	CTNNBL1	NM_001281495.2		c.245+4380A>G		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.326+4380A>G		intron	N/A	ENSP00000355050.6
	CTNNBL1	ENST00000628103.2	TSL:2	c.245+4380A>G		intron	N/A	ENSP00000487198.1
	CTNNBL1	ENST00000447935.3	TSL:5	c.245+4380A>G		intron	N/A	ENSP00000394464.1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23668 AN: 151852 Hom.: 3442 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.0990

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.0299

Gnomad SAS AF: 0.0338

Gnomad FIN AF: 0.0775

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.0647

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.156 AC: 23713 AN: 151970 Hom.: 3450 Cov.: 32 AF XY: 0.152 AC XY: 11302 AN XY: 74268

African (AFR) AF: 0.386 AC: 15999 AN: 41426

American (AMR) AF: 0.0990 AC: 1512 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3468

East Asian (EAS) AF: 0.0300 AC: 155 AN: 5166

South Asian (SAS) AF: 0.0337 AC: 162 AN: 4814

European-Finnish (FIN) AF: 0.0775 AC: 818 AN: 10556

Middle Eastern (MID) AF: 0.0959 AC: 28 AN: 292

European-Non Finnish (NFE) AF: 0.0647 AC: 4397 AN: 67958

Other (OTH) AF: 0.142 AC: 299 AN: 2110

Alfa AF: 0.122 Hom.: 364

Bravo AF: 0.168

Asia WGS AF: 0.0620 AC: 216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.74
PhyloP100		-0.20
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: rs2344481; hg19: chr20-36370266;