20-37768027-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_030877.5(CTNNBL1):c.733C>G(p.Leu245Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000468 in 1,613,942 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (2 hom.)
• Consequence: CTNNBL1 NM_030877.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.986

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01103279).
• BP6: Variant 20-37768027-C-G is Benign according to our data. Variant chr20-37768027-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 725816.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNBL1	NM_030877.5	c.733C>G	p.Leu245Val	missense_variant	7/16	ENST00000361383.11
CTNNBL1	NM_001281495.2	c.652C>G	p.Leu218Val	missense_variant	8/17
CTNNBL1	XM_024451947.2	c.652C>G	p.Leu218Val	missense_variant	8/17
CTNNBL1	XM_011528917.3	c.403C>G	p.Leu135Val	missense_variant	5/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNBL1	ENST00000361383.11	c.733C>G	p.Leu245Val	missense_variant	7/16	1	NM_030877.5	P1
CTNNBL1	ENST00000373473.5	c.172C>G	p.Leu58Val	missense_variant	4/13	1
CTNNBL1	ENST00000628103.2	c.652C>G	p.Leu218Val	missense_variant	8/17	2
CTNNBL1	ENST00000473857.5	n.1817C>G		non_coding_transcript_exon_variant	6/16	2

Frequencies

GnomAD3 genomes AF: 0.00215 AC: 327 AN: 152094 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00730

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000983

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000744 AC: 187 AN: 251298 Hom.: 1 AF XY: 0.000508 AC XY: 69 AN XY: 135810

Gnomad AFR exome AF: 0.00941

Gnomad AMR exome AF: 0.000636

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000880

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000293 AC: 428 AN: 1461730 Hom.: 2 Cov.: 30 AF XY: 0.000245 AC XY: 178 AN XY: 727174

Gnomad4 AFR exome AF: 0.00869

Gnomad4 AMR exome AF: 0.000648

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000468

Gnomad4 OTH exome AF: 0.000745

GnomAD4 genome AF: 0.00215 AC: 327 AN: 152212 Hom.: 2 Cov.: 32 AF XY: 0.00200 AC XY: 149 AN XY: 74410

Gnomad4 AFR AF: 0.00727

Gnomad4 AMR AF: 0.000982

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000608 Hom.: 0

Bravo AF: 0.00283

ExAC AF: 0.000832 AC: 101

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

Invitae

Apr 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Uncertain	-0.010
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D;D;.;D
MetaRNN	Benign	0.011	T;T;T;T;T
MetaSVM	Benign	-0.49	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.69	T
Sift4G	Uncertain	0.014	D;D;D;D;D
Polyphen		0.98, 0.96	.;.;D;.;D
Vest4		0.63
MVP		0.55
MPC		0.57
ClinPred		0.058	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.61
gMVP		0.78

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: rs186475150; hg19: chr20-36396429;