rs4811196

chr20-37841292-G-Achr20-37841292-G-Cchr20-37841292-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030877.5(CTNNBL1):c.1312-1047G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 152,168 control chromosomes in the GnomAD database, including 50,820 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 0.82 (50820 hom., cov: 32)
• Consequence: CTNNBL1 NM_030877.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.497

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNBL1	NM_030877.5	c.1312-1047G>A		intron_variant		ENST00000361383.11
CTNNBL1	NM_001281495.2	c.1231-1047G>A		intron_variant
CTNNBL1	XM_011528917.3	c.982-1047G>A		intron_variant
CTNNBL1	XM_024451947.2	c.1231-1047G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNBL1	ENST00000361383.11	c.1312-1047G>A		intron_variant		1	NM_030877.5	P1

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124165 AN: 152050 Hom.: 50764 Cov.: 32

Gnomad AFR AF: 0.822

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.896

Gnomad EAS AF: 0.862

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.848

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

GnomAD4 genome AF: 0.817 AC: 124280 AN: 152168 Hom.: 50820 Cov.: 32 AF XY: 0.815 AC XY: 60626 AN XY: 74382

Gnomad4 AFR AF: 0.822

Gnomad4 AMR AF: 0.873

Gnomad4 ASJ AF: 0.896

Gnomad4 EAS AF: 0.862

Gnomad4 SAS AF: 0.865

Gnomad4 FIN AF: 0.726

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.850

Alfa AF: 0.810 Hom.: 75222

Bravo AF: 0.828

Asia WGS AF: 0.875 AC: 3042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.1
Dann	Benign	0.74

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: rs4811196; hg19: chr20-36469694;