20-37804886-T-C

Variant names:

• chr20-37804886-T-C
• rs2281148
• NM_030877.5:c.1213+1838T>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.1213+1838T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,170 control chromosomes in the GnomAD database, including 3,915 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 0.20 (3915 hom., cov: 33)
• Consequence: CTNNBL1 NM_030877.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.52
• Publications: 2 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=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNBL1	NM_030877.5	MANE Select	c.1213+1838T>C		intron	N/A	NP_110517.2
	CTNNBL1	NM_001281495.2		c.1132+1838T>C		intron	N/A	NP_001268424.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNBL1	ENST00000361383.11	TSL:1 MANE Select	c.1213+1838T>C		intron	N/A	ENSP00000355050.6
	CTNNBL1	ENST00000628103.2	TSL:2	c.1132+1838T>C		intron	N/A	ENSP00000487198.1
	CTNNBL1	ENST00000373473.5	TSL:1	c.652+1838T>C		intron	N/A	ENSP00000362572.1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30761 AN: 152052 Hom.: 3912 Cov.: 33

Gnomad AFR AF: 0.0528

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.202 AC: 30778 AN: 152170 Hom.: 3915 Cov.: 33 AF XY: 0.207 AC XY: 15421 AN XY: 74392

African (AFR) AF: 0.0527 AC: 2191 AN: 41536

American (AMR) AF: 0.278 AC: 4260 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 734 AN: 3466

East Asian (EAS) AF: 0.418 AC: 2160 AN: 5166

South Asian (SAS) AF: 0.273 AC: 1317 AN: 4816

European-Finnish (FIN) AF: 0.268 AC: 2833 AN: 10578

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16453 AN: 67984

Other (OTH) AF: 0.207 AC: 437 AN: 2116

Alfa AF: 0.228 Hom.: 1964

Bravo AF: 0.199

Asia WGS AF: 0.316 AC: 1099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	10
DANN	Benign	0.46
PhyloP100		2.5
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: rs2281148; hg19: chr20-36433288;