rs11552054

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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 (★★). Synonymous variant affecting the same amino acid position (i.e. L180L) has been classified as Likely 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:9

Conservation

PhyloP100: 1.04

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

CTNNA1-related diffuse gastric and lobular breast cancer syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
patterned macular dystrophy 2
Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
patterned macular dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary nonpolyposis colon cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

CTNNA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 415357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

GnomAD2 exomes

AF:

0.0323

AC:

8124

AN:

251314

AF XY:

0.0356

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 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

African (AFR)

AF:

0.00720

AC:

241

AN:

33476

American (AMR)

AF:

0.0164

AC:

734

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0555

AC:

1450

AN:

26126

East Asian (EAS)

AF:

0.000176

AC:

AN:

39680

South Asian (SAS)

AF:

0.0638

AC:

5496

AN:

86204

European-Finnish (FIN)

AF:

0.0191

AC:

1022

AN:

53402

Middle Eastern (MID)

AF:

0.0756

AC:

436

AN:

5766

European-Non Finnish (NFE)

AF:

0.0421

AC:

46783

AN:

1111680

Other (OTH)

AF:

0.0378

AC:

2281

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

2699

5398

8096

10795

13494

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1782

3564

5346

7128

8910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0279

AC:

4250

AN:

152292

Hom.:

Cov.:

AF XY:

0.0268

AC XY:

1995

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00804

AC:

334

AN:

41568

American (AMR)

AF:

0.0231

AC:

354

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0548

AC:

190

AN:

3470

East Asian (EAS)

AF:

0.000579

AC:

AN:

5178

South Asian (SAS)

AF:

0.0523

AC:

252

AN:

4818

European-Finnish (FIN)

AF:

0.0172

AC:

183

AN:

10614

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0420

AC:

2855

AN:

68014

Other (OTH)

AF:

0.0241

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

213

426

638

851

1064

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0371

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:9

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

- -

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Benign

Review Status:criteria provided, single submitter

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

- -

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 nonpolyposis colon cancer

Benign:1

Apr 29, 2021

Department of Pathology and Laboratory Medicine, Sinai Health System

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

(source)

DANN

Benign

0.74

PhyloP100

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over