NM_030877.5:c.751-831A>G

Variant names:

• chr20-37776514-A-G
• rs238302
• NM_030877.5:c.751-831A>G

Variant summary

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

The NM_030877.5(CTNNBL1):​c.751-831A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 152,052 control chromosomes in the GnomAD database, including 34,775 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 0.68 (34775 hom., cov: 32)
• Consequence: CTNNBL1 NM_030877.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.510
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNBL1	NM_030877.5	c.751-831A>G		intron_variant	Intron 7 of 15	ENST00000361383.11	NP_110517.2
CTNNBL1	NM_001281495.2	c.670-831A>G		intron_variant	Intron 8 of 16		NP_001268424.1
CTNNBL1	XM_024451947.2	c.670-831A>G		intron_variant	Intron 8 of 16		XP_024307715.1
CTNNBL1	XM_011528917.3	c.421-831A>G		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.751-831A>G		intron_variant	Intron 7 of 15	1	NM_030877.5	ENSP00000355050.6
CTNNBL1	ENST00000628103.2	c.670-831A>G		intron_variant	Intron 8 of 16	2		ENSP00000487198.1
CTNNBL1	ENST00000373473.5	c.190-831A>G		intron_variant	Intron 4 of 12	1		ENSP00000362572.1
CTNNBL1	ENST00000473857.5	n.1835-831A>G		intron_variant	Intron 6 of 15	2

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102618 AN: 151934 Hom.: 34747 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.790

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.707

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

GnomAD4 genome AF: 0.675 AC: 102696 AN: 152052 Hom.: 34775 Cov.: 32 AF XY: 0.677 AC XY: 50305 AN XY: 74318

African (AFR) AF: 0.642 AC: 26622 AN: 41450

American (AMR) AF: 0.667 AC: 10191 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2699 AN: 3460

East Asian (EAS) AF: 0.839 AC: 4354 AN: 5188

South Asian (SAS) AF: 0.736 AC: 3542 AN: 4814

European-Finnish (FIN) AF: 0.640 AC: 6755 AN: 10558

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.678 AC: 46086 AN: 67980

Other (OTH) AF: 0.710 AC: 1502 AN: 2116

Alfa AF: 0.681 Hom.: 58892

Bravo AF: 0.674

Asia WGS AF: 0.801 AC: 2784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.40
DANN	Benign	0.26
PhyloP100		-0.51
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: rs238302; hg19: chr20-36404916;