rs45500793

Positions:

• chr20-37859883-G-A
• chr20-37859883-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_030877.5(CTNNBL1):​c.1393-16G>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 0.00719 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65

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 -8 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNBL1	NM_030877.5	c.1393-16G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000361383.11
CTNNBL1	NM_001281495.2	c.1312-16G>A		splice_polypyrimidine_tract_variant, intron_variant
CTNNBL1	XM_011528917.3	c.1063-16G>A		splice_polypyrimidine_tract_variant, intron_variant
CTNNBL1	XM_024451947.2	c.1312-16G>A		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNBL1	ENST00000361383.11	c.1393-16G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_030877.5	P1

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

GnomAD3 exomes AF: 0.00424 AC: 1062 AN: 250252 Hom.: 0 AF XY: 0.00426 AC XY: 576 AN XY: 135274

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 SAS exome AF: 0.000361

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

Gnomad4 AFR exome AF: 0.00131

Gnomad4 AMR exome AF: 0.00284

Gnomad4 ASJ exome AF: 0.00242

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000372

Gnomad4 FIN exome AF: 0.00204

Gnomad4 NFE exome AF: 0.00918

Gnomad4 OTH exome AF: 0.00515

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

Gnomad4 AFR AF: 0.00123

Gnomad4 AMR AF: 0.00445

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00254

Gnomad4 NFE AF: 0.00797

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00242 Hom.: 1

Bravo AF: 0.00470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.9
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs45500793; hg19: chr20-36488285;