20-37871911-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030877.5(CTNNBL1):c.1604-14C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 1,610,764 control chromosomes in the GnomAD database, including 114,911 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (8367 hom., cov: 31)
  • Exomes 𝑓: 0.38 (106544 hom.)
• Consequence: CTNNBL1 NM_030877.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0600

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 20-37871911-C-A is Benign according to our data. Variant chr20-37871911-C-A is described in ClinVar as [Benign]. Clinvar id is 2688114.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNBL1	NM_030877.5	c.1604-14C>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000361383.11
CTNNBL1	NM_001281495.2	c.1523-14C>A		splice_polypyrimidine_tract_variant, intron_variant
CTNNBL1	XM_011528917.3	c.1274-14C>A		splice_polypyrimidine_tract_variant, intron_variant
CTNNBL1	XM_024451947.2	c.1523-14C>A		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNBL1	ENST00000361383.11	c.1604-14C>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_030877.5	P1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47673 AN: 151802 Hom.: 8369 Cov.: 31

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.366

GnomAD3 exomes AF: 0.351 AC: 87621 AN: 249530 Hom.: 16633 AF XY: 0.362 AC XY: 48920 AN XY: 135010

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.227

Gnomad ASJ exome AF: 0.552

Gnomad EAS exome AF: 0.391

Gnomad SAS exome AF: 0.427

Gnomad FIN exome AF: 0.247

Gnomad NFE exome AF: 0.388

Gnomad OTH exome AF: 0.382

GnomAD4 exome AF: 0.377 AC: 550068 AN: 1458844 Hom.: 106544 Cov.: 31 AF XY: 0.379 AC XY: 275258 AN XY: 725794

Gnomad4 AFR exome AF: 0.177

Gnomad4 AMR exome AF: 0.240

Gnomad4 ASJ exome AF: 0.550

Gnomad4 EAS exome AF: 0.406

Gnomad4 SAS exome AF: 0.422

Gnomad4 FIN exome AF: 0.255

Gnomad4 NFE exome AF: 0.386

Gnomad4 OTH exome AF: 0.381

GnomAD4 genome AF: 0.314 AC: 47680 AN: 151920 Hom.: 8367 Cov.: 31 AF XY: 0.310 AC XY: 23048 AN XY: 74284

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.365

Alfa AF: 0.381 Hom.: 13466

Bravo AF: 0.310

Asia WGS AF: 0.421 AC: 1465 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 52% of patients studied by a panel of primary immunodeficiencies. Number of patients: 49. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	11
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs717599; hg19: chr20-36500313; COSMIC: COSV63744222;