20-37842380-A-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_030877.5(CTNNBL1):c.1353A>G(p.Ala451=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000466 in 1,613,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00060 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (0 hom.)
• Consequence: CTNNBL1 NM_030877.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.377

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 20-37842380-A-G is Benign according to our data. Variant chr20-37842380-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2652306.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.377 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNBL1	NM_030877.5	c.1353A>G	p.Ala451=	synonymous_variant	13/16	ENST00000361383.11
CTNNBL1	NM_001281495.2	c.1272A>G	p.Ala424=	synonymous_variant	14/17
CTNNBL1	XM_024451947.2	c.1272A>G	p.Ala424=	synonymous_variant	14/17
CTNNBL1	XM_011528917.3	c.1023A>G	p.Ala341=	synonymous_variant	11/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNBL1	ENST00000361383.11	c.1353A>G	p.Ala451=	synonymous_variant	13/16	1	NM_030877.5	P1

Frequencies

GnomAD3 genomes AF: 0.000598 AC: 91 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000764

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000601 AC: 151 AN: 251396 Hom.: 0 AF XY: 0.000626 AC XY: 85 AN XY: 135864

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.000878

Gnomad NFE exome AF: 0.00102

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000452 AC: 661 AN: 1461688 Hom.: 0 Cov.: 29 AF XY: 0.000469 AC XY: 341 AN XY: 727162

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000268

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.000842

Gnomad4 NFE exome AF: 0.000514

Gnomad4 OTH exome AF: 0.000331

GnomAD4 genome AF: 0.000598 AC: 91 AN: 152298 Hom.: 0 Cov.: 32 AF XY: 0.000618 AC XY: 46 AN XY: 74460

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.000764

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000569 Hom.: 0

Bravo AF: 0.000431

EpiCase AF: 0.000872

EpiControl AF: 0.000534

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

CTNNBL1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	8.6
Dann	Benign	0.71

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: rs147450818; hg19: chr20-36470782;