rs11552054

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001903.5(CTNNA1):c.540A>C(p.Leu180Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 1,613,716 control chromosomes in the GnomAD database, including 1,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 90 hom., cov: 32)

Exomes 𝑓: 0.040 ( 1418 hom. )

Consequence

CTNNA1
NM_001903.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.04

Variant links:

Genes affected

CTNNA1 (HGNC:2509): (catenin alpha 1) This gene encodes a member of the catenin family of proteins that play an important role in cell adhesion process by connecting cadherins located on the plasma membrane to the actin filaments inside the cell. The encoded mechanosensing protein contains three vinculin homology domains and undergoes conformational changes in response to cytoskeletal tension, resulting in the reconfiguration of cadherin-actin filament connections. Certain mutations in this gene cause butterfly-shaped pigment dystrophy. [provided by RefSeq, May 2016]

CTNNA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 5-138812254-A-C is Benign according to our data. Variant chr5-138812254-A-C is described in ClinVar as [Benign]. Clinvar id is 415357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-138812254-A-C is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA1	NM_001903.5 link	c.540A>C	p.Leu180Leu	synonymous_variant	Exon 5 of 18	ENST00000302763.12	NP_001894.2	P35221-1A0A384MDY0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA1	ENST00000302763.12 link	c.540A>C	p.Leu180Leu	synonymous_variant	Exon 5 of 18	1	NM_001903.5	ENSP00000304669.7		P35221-1

Frequencies

GnomAD3 genomes

AF:

0.0279

AC:

4249

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00806

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0232

Gnomad ASJ

AF:

0.0548

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0523

Gnomad FIN

AF:

0.0172

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0420

Gnomad OTH

AF:

0.0244

GnomAD3 exomes

AF:

0.0323

AC:

8124

AN:

251314

Hom.:

191

AF XY:

0.0356

AC XY:

4833

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.00812

Gnomad AMR exome

AF:

0.0145

Gnomad ASJ exome

AF:

0.0543

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.0620

Gnomad FIN exome

AF:

0.0151

Gnomad NFE exome

AF:

0.0393

Gnomad OTH exome

AF:

0.0393

GnomAD4 exome

AF:

0.0400

AC:

58450

AN:

1461424

Hom.:

1418

Cov.:

AF XY:

0.0412

AC XY:

29961

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.00720

Gnomad4 AMR exome

AF:

0.0164

Gnomad4 ASJ exome

AF:

0.0555

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0638

Gnomad4 FIN exome

AF:

0.0191

Gnomad4 NFE exome

AF:

0.0421

Gnomad4 OTH exome

AF:

0.0378

GnomAD4 genome

AF:

0.0279

AC:

4250

AN:

152292

Hom.:

Cov.:

AF XY:

0.0268

AC XY:

1995

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00804

Gnomad4 AMR

AF:

0.0231

Gnomad4 ASJ

AF:

0.0548

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0523

Gnomad4 FIN

AF:

0.0172

Gnomad4 NFE

AF:

0.0420

Gnomad4 OTH

AF:

0.0241

Alfa

AF:

0.0373

Hom.:

Bravo

AF:

0.0264

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.0446

EpiControl

AF:

0.0402

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary diffuse gastric adenocarcinoma

Benign:1

Oct 10, 2024

Myriad Genetics, Inc.

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -

Hereditary cancer-predisposing syndrome

Benign:1

Mar 26, 2019

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.5

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over