rs8126174

Variant names:

• chr20-37797063-A-G
• rs8126174
• NM_030877.5:c.1032-5804A>G

Your query was ambiguous. Multiple possible variants found:

• chr20-37797063-A-G
• chr20-37797063-A-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.1032-5804A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 151,954 control chromosomes in the GnomAD database, including 9,709 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 0.35 (9709 hom., cov: 31)
• Consequence: CTNNBL1 NM_030877.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNBL1	NM_030877.5	c.1032-5804A>G		intron_variant	Intron 10 of 15	ENST00000361383.11	NP_110517.2
CTNNBL1	NM_001281495.2	c.951-5804A>G		intron_variant	Intron 11 of 16		NP_001268424.1
CTNNBL1	XM_024451947.2	c.951-5804A>G		intron_variant	Intron 11 of 16		XP_024307715.1
CTNNBL1	XM_011528917.3	c.702-5804A>G		intron_variant	Intron 8 of 13		XP_011527219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNBL1	ENST00000361383.11	c.1032-5804A>G		intron_variant	Intron 10 of 15	1	NM_030877.5	ENSP00000355050.6
CTNNBL1	ENST00000628103.2	c.951-5804A>G		intron_variant	Intron 11 of 16	2		ENSP00000487198.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52856 AN: 151836 Hom.: 9714 Cov.: 31

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.348 AC: 52849 AN: 151954 Hom.: 9709 Cov.: 31 AF XY: 0.345 AC XY: 25659 AN XY: 74276

African (AFR) AF: 0.240 AC: 9929 AN: 41454

American (AMR) AF: 0.308 AC: 4697 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1920 AN: 3468

East Asian (EAS) AF: 0.480 AC: 2477 AN: 5164

South Asian (SAS) AF: 0.436 AC: 2095 AN: 4802

European-Finnish (FIN) AF: 0.317 AC: 3348 AN: 10552

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.399 AC: 27090 AN: 67942

Other (OTH) AF: 0.375 AC: 788 AN: 2102

Alfa AF: 0.360 Hom.: 3108

Bravo AF: 0.340

Asia WGS AF: 0.456 AC: 1585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.36
PhyloP100		-0.29
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: rs8126174; hg19: chr20-36425465;