NM_030877.5:c.1393-16G>A

Variant names:

• chr20-37859883-G-A
• rs45500793
• NM_030877.5:c.1393-16G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_030877.5(CTNNBL1):​c.1393-16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00719 in 1,612,994 control chromosomes in the GnomAD database, including 62 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 0.0047 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0075 (61 hom.)
• Consequence: CTNNBL1 NM_030877.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BS2: High Homozygotes in GnomAdExome4 at 61 AR,Unknown gene

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.1393-16G>A		intron	N/A	NP_110517.2
	CTNNBL1	NM_001281495.2		c.1312-16G>A		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.1393-16G>A		intron	N/A	ENSP00000355050.6
	CTNNBL1	ENST00000628103.2	TSL:2	c.1312-16G>A		intron	N/A	ENSP00000487198.1
	CTNNBL1	ENST00000373473.5	TSL:1	c.832-16G>A		intron	N/A	ENSP00000362572.1

Frequencies

GnomAD3 genomes AF: 0.00467 AC: 710 AN: 152130 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00254

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00797

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00424 AC: 1062 AN: 250252 AF XY: 0.00426

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.00311

Gnomad ASJ exome AF: 0.00220

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00191

Gnomad NFE exome AF: 0.00737

Gnomad OTH exome AF: 0.00426

GnomAD4 exome AF: 0.00746 AC: 10895 AN: 1460746 Hom.: 61 Cov.: 31 AF XY: 0.00714 AC XY: 5189 AN XY: 726592

African (AFR) AF: 0.00131 AC: 44 AN: 33466

American (AMR) AF: 0.00284 AC: 127 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.00242 AC: 63 AN: 26076

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39678

South Asian (SAS) AF: 0.000372 AC: 32 AN: 86096

European-Finnish (FIN) AF: 0.00204 AC: 109 AN: 53314

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5764

European-Non Finnish (NFE) AF: 0.00918 AC: 10200 AN: 1111360

Other (OTH) AF: 0.00515 AC: 311 AN: 60348

GnomAD4 genome AF: 0.00466 AC: 710 AN: 152248 Hom.: 1 Cov.: 32 AF XY: 0.00434 AC XY: 323 AN XY: 74452

African (AFR) AF: 0.00123 AC: 51 AN: 41540

American (AMR) AF: 0.00445 AC: 68 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00254 AC: 27 AN: 10616

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00797 AC: 542 AN: 68012

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00242 Hom.: 1

Bravo AF: 0.00470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.9
DANN	Benign	0.74
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism

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: rs45500793; hg19: chr20-36488285;