rs2235460

Variant names:

• chr20-37852641-G-A
• rs2235460
• NM_030877.5:c.1393-7258G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-37852641-G-A
• chr20-37852641-G-C

Variant summary

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

The NM_030877.5(CTNNBL1):​c.1393-7258G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 152,030 control chromosomes in the GnomAD database, including 10,349 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 0.36 (10349 hom., cov: 32)
• Consequence: CTNNBL1 NM_030877.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNBL1	NM_030877.5	c.1393-7258G>A		intron_variant	Intron 13 of 15	ENST00000361383.11	NP_110517.2
CTNNBL1	NM_001281495.2	c.1312-7258G>A		intron_variant	Intron 14 of 16		NP_001268424.1
CTNNBL1	XM_024451947.2	c.1312-7258G>A		intron_variant	Intron 14 of 16		XP_024307715.1
CTNNBL1	XM_011528917.3	c.1063-7258G>A		intron_variant	Intron 11 of 13		XP_011527219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNBL1	ENST00000361383.11	c.1393-7258G>A		intron_variant	Intron 13 of 15	1	NM_030877.5	ENSP00000355050.6
CTNNBL1	ENST00000628103.2	c.1312-7258G>A		intron_variant	Intron 14 of 16	2		ENSP00000487198.1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55202 AN: 151912 Hom.: 10348 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.363 AC: 55231 AN: 152030 Hom.: 10349 Cov.: 32 AF XY: 0.358 AC XY: 26573 AN XY: 74294

African (AFR) AF: 0.344 AC: 14278 AN: 41448

American (AMR) AF: 0.324 AC: 4944 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1871 AN: 3466

East Asian (EAS) AF: 0.402 AC: 2078 AN: 5168

South Asian (SAS) AF: 0.428 AC: 2061 AN: 4812

European-Finnish (FIN) AF: 0.243 AC: 2566 AN: 10554

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

European-Non Finnish (NFE) AF: 0.387 AC: 26310 AN: 67984

Other (OTH) AF: 0.402 AC: 850 AN: 2116

Alfa AF: 0.378 Hom.: 18110

Bravo AF: 0.365

Asia WGS AF: 0.433 AC: 1507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.64
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: rs2235460; hg19: chr20-36481043;