20-37859883-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_030877.5(CTNNBL1):​c.1393-16G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 1,612,982 control chromosomes in the GnomAD database, including 240 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 0.011 (10 hom., cov: 32)
  • Exomes 𝑓: 0.016 (230 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0109 (1665/152252) while in subpopulation NFE AF = 0.017 (1153/68016). AF 95% confidence interval is 0.0161. There are 10 homozygotes in GnomAd4. There are 769 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 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>T		intron	N/A	NP_110517.2
	CTNNBL1	NM_001281495.2		c.1312-16G>T		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>T		intron	N/A	ENSP00000355050.6
	CTNNBL1	ENST00000628103.2	TSL:2	c.1312-16G>T		intron	N/A	ENSP00000487198.1
	CTNNBL1	ENST00000373473.5	TSL:1	c.832-16G>T		intron	N/A	ENSP00000362572.1

Frequencies

GnomAD3 genomes AF: 0.0109 AC: 1664 AN: 152134 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00345

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00556

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0169

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00963 AC: 2410 AN: 250252 AF XY: 0.00954

Gnomad AFR exome AF: 0.00376

Gnomad AMR exome AF: 0.0102

Gnomad ASJ exome AF: 0.00479

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00465

Gnomad NFE exome AF: 0.0150

Gnomad OTH exome AF: 0.0121

GnomAD4 exome AF: 0.0160 AC: 23310 AN: 1460730 Hom.: 230 Cov.: 31 AF XY: 0.0154 AC XY: 11196 AN XY: 726580

African (AFR) AF: 0.00296 AC: 99 AN: 33466

American (AMR) AF: 0.0101 AC: 451 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.00499 AC: 130 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00233 AC: 201 AN: 86096

European-Finnish (FIN) AF: 0.00506 AC: 270 AN: 53312

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5764

European-Non Finnish (NFE) AF: 0.0191 AC: 21266 AN: 1111350

Other (OTH) AF: 0.0145 AC: 878 AN: 60346

GnomAD4 genome AF: 0.0109 AC: 1665 AN: 152252 Hom.: 10 Cov.: 32 AF XY: 0.0103 AC XY: 769 AN XY: 74454

African (AFR) AF: 0.00344 AC: 143 AN: 41540

American (AMR) AF: 0.0164 AC: 251 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4822

European-Finnish (FIN) AF: 0.00556 AC: 59 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0170 AC: 1153 AN: 68016

Other (OTH) AF: 0.0132 AC: 28 AN: 2114

Alfa AF: 0.00466 Hom.: 1

Bravo AF: 0.0116

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.6
DANN	Benign	0.70
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;