rs6013029

Variant names:

• chr20-37771178-G-T
• rs6013029
• NM_030877.5:c.750+3134G>T

Variant summary

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

The NM_030877.5(CTNNBL1):​c.750+3134G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,160 control chromosomes in the GnomAD database, including 1,700 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 0.11 (1700 hom., cov: 32)
• Consequence: CTNNBL1 NM_030877.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154
• Publications: 30 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNBL1	NM_030877.5	c.750+3134G>T		intron_variant	Intron 7 of 15	ENST00000361383.11	NP_110517.2
CTNNBL1	NM_001281495.2	c.669+3134G>T		intron_variant	Intron 8 of 16		NP_001268424.1
CTNNBL1	XM_024451947.2	c.669+3134G>T		intron_variant	Intron 8 of 16		XP_024307715.1
CTNNBL1	XM_011528917.3	c.420+3134G>T		intron_variant	Intron 5 of 13		XP_011527219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNBL1	ENST00000361383.11	c.750+3134G>T		intron_variant	Intron 7 of 15	1	NM_030877.5	ENSP00000355050.6
CTNNBL1	ENST00000628103.2	c.669+3134G>T		intron_variant	Intron 8 of 16	2		ENSP00000487198.1
CTNNBL1	ENST00000373473.5	c.189+3134G>T		intron_variant	Intron 4 of 12	1		ENSP00000362572.1
CTNNBL1	ENST00000473857.5	n.1834+3134G>T		intron_variant	Intron 6 of 15	2

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17282 AN: 152042 Hom.: 1693 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.0677

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.0308

Gnomad FIN AF: 0.0677

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0554

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.114 AC: 17319 AN: 152160 Hom.: 1700 Cov.: 32 AF XY: 0.111 AC XY: 8284 AN XY: 74408

African (AFR) AF: 0.268 AC: 11121 AN: 41470

American (AMR) AF: 0.0676 AC: 1034 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3470

East Asian (EAS) AF: 0.0100 AC: 52 AN: 5184

South Asian (SAS) AF: 0.0309 AC: 149 AN: 4826

European-Finnish (FIN) AF: 0.0677 AC: 718 AN: 10606

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0555 AC: 3771 AN: 68000

Other (OTH) AF: 0.111 AC: 234 AN: 2114

Alfa AF: 0.0738 Hom.: 894

Bravo AF: 0.121

Asia WGS AF: 0.0410 AC: 143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.49
PhyloP100		0.15
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: rs6013029; hg19: chr20-36399580;