rs147450818

Variant names:

• chr20-37842380-A-C
• rs147450818
• NM_030877.5:c.1353A>C

Your query was ambiguous. Multiple possible variants found:

• chr20-37842380-A-C
• chr20-37842380-A-G
• chr20-37842380-A-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_030877.5(CTNNBL1):​c.1353A>C​(p.Ala451Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A451A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTNNBL1 NM_030877.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=0.377 with no splicing effect.

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.1353A>C	p.Ala451Ala	synonymous	Exon 13 of 16	NP_110517.2
	CTNNBL1	NM_001281495.2		c.1272A>C	p.Ala424Ala	synonymous	Exon 14 of 17	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.1353A>C	p.Ala451Ala	synonymous	Exon 13 of 16	ENSP00000355050.6	Q8WYA6-1
	CTNNBL1	ENST00000628103.2	TSL:2	c.1272A>C	p.Ala424Ala	synonymous	Exon 14 of 17	ENSP00000487198.1	Q8WYA6-4
	CTNNBL1	ENST00000373473.5	TSL:1	c.792A>C	p.Ala264Ala	synonymous	Exon 10 of 13	ENSP00000362572.1	Q8WYA6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	8.2
DANN	Benign	0.71
PhyloP100		0.38

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: rs147450818; hg19: chr20-36470782;