rs6020712

Variant names:

• chr20-37758210-G-A
• rs6020712
• NM_030877.5:c.564+554G>A

Variant summary

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

The NM_030877.5(CTNNBL1):​c.564+554G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,208 control chromosomes in the GnomAD database, including 1,769 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 0.12 (1769 hom., cov: 32)
• Consequence: CTNNBL1 NM_030877.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.473
• Publications: 11 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 (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNBL1	NM_030877.5	c.564+554G>A		intron_variant	Intron 5 of 15	ENST00000361383.11	NP_110517.2
CTNNBL1	NM_001281495.2	c.483+554G>A		intron_variant	Intron 6 of 16		NP_001268424.1
CTNNBL1	XM_024451947.2	c.483+554G>A		intron_variant	Intron 6 of 16		XP_024307715.1
CTNNBL1	XM_011528917.3	c.234+554G>A		intron_variant	Intron 3 of 13		XP_011527219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNBL1	ENST00000361383.11	c.564+554G>A		intron_variant	Intron 5 of 15	1	NM_030877.5	ENSP00000355050.6
CTNNBL1	ENST00000628103.2	c.483+554G>A		intron_variant	Intron 6 of 16	2		ENSP00000487198.1
CTNNBL1	ENST00000447935.3	c.483+554G>A		intron_variant	Intron 6 of 6	5		ENSP00000394464.1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17560 AN: 152090 Hom.: 1763 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0685

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.0307

Gnomad FIN AF: 0.0676

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0555

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.116 AC: 17596 AN: 152208 Hom.: 1769 Cov.: 32 AF XY: 0.113 AC XY: 8398 AN XY: 74422

African (AFR) AF: 0.274 AC: 11369 AN: 41490

American (AMR) AF: 0.0684 AC: 1047 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3472

East Asian (EAS) AF: 0.0100 AC: 52 AN: 5186

South Asian (SAS) AF: 0.0307 AC: 148 AN: 4822

European-Finnish (FIN) AF: 0.0676 AC: 717 AN: 10610

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0556 AC: 3779 AN: 68006

Other (OTH) AF: 0.115 AC: 243 AN: 2114

Alfa AF: 0.0701 Hom.: 691

Bravo AF: 0.123

Asia WGS AF: 0.0420 AC: 147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.46
PhyloP100		-0.47
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: rs6020712; hg19: chr20-36386612;