rs1059110

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001903.5(CTNNA1):c.2220G>A(p.Ser740Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,610,028 control chromosomes in the GnomAD database, including 70,975 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. S740S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.31 ( 7853 hom., cov: 32)

Exomes 𝑓: 0.29 ( 63122 hom. )

Consequence

CTNNA1
NM_001903.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.681

Publications

27 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 5-138930857-G-A is Benign according to our data. Variant chr5-138930857-G-A is described in ClinVar as Benign. ClinVar VariationId is 820919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.681 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA1	NM_001903.5 link	c.2220G>A	p.Ser740Ser	synonymous_variant	Exon 16 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.2220G>A	p.Ser740Ser	synonymous_variant	Exon 16 of 18	1	NM_001903.5	ENSP00000304669.7		P35221-1

Frequencies

GnomAD3 genomes

AF:

0.314

AC:

47726

AN:

151918

Hom.:

7835

Cov.:

show subpopulations

Gnomad AFR

AF:

0.407

Gnomad AMI

AF:

0.317

Gnomad AMR

AF:

0.251

Gnomad ASJ

AF:

0.337

Gnomad EAS

AF:

0.00616

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.295

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.304

Gnomad OTH

AF:

0.288

GnomAD2 exomes

AF:

0.274

AC:

68952

AN:

251416

AF XY:

0.273

show subpopulations

Gnomad AFR exome

AF:

0.406

Gnomad AMR exome

AF:

0.271

Gnomad ASJ exome

AF:

0.323

Gnomad EAS exome

AF:

0.00299

Gnomad FIN exome

AF:

0.298

Gnomad NFE exome

AF:

0.295

Gnomad OTH exome

AF:

0.275

GnomAD4 exome

AF:

0.287

AC:

418876

AN:

1457992

Hom.:

63122

Cov.:

AF XY:

0.288

AC XY:

208685

AN XY:

725582

show subpopulations

African (AFR)

AF:

0.413

AC:

13766

AN:

33366

American (AMR)

AF:

0.268

AC:

11963

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.328

AC:

8570

AN:

26112

East Asian (EAS)

AF:

0.00927

AC:

368

AN:

39698

South Asian (SAS)

AF:

0.263

AC:

22659

AN:

86166

European-Finnish (FIN)

AF:

0.304

AC:

16258

AN:

53416

Middle Eastern (MID)

AF:

0.267

AC:

1538

AN:

5764

European-Non Finnish (NFE)

AF:

0.295

AC:

326778

AN:

1108480

Other (OTH)

AF:

0.282

AC:

16976

AN:

60274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

13429

26858

40288

53717

67146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10608

21216

31824

42432

53040

<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:

0.314

AC:

47784

AN:

152036

Hom.:

7853

Cov.:

AF XY:

0.309

AC XY:

22995

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.407

AC:

16880

AN:

41454

American (AMR)

AF:

0.250

AC:

3820

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.337

AC:

1171

AN:

3470

East Asian (EAS)

AF:

0.00637

AC:

AN:

5180

South Asian (SAS)

AF:

0.236

AC:

1137

AN:

4818

European-Finnish (FIN)

AF:

0.295

AC:

3119

AN:

10572

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.304

AC:

20643

AN:

67962

Other (OTH)

AF:

0.283

AC:

598

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1662

3324

4987

6649

8311

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

472

944

1416

1888

2360

<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:

0.302

Hom.:

11236

Bravo

AF:

0.312

Asia WGS

AF:

0.135

AC:

470

AN:

3478

EpiCase

AF:

0.294

EpiControl

AF:

0.283

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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 cancer-predisposing syndrome

Benign:2

Nov 08, 2018

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. -

May 28, 2024

Hereditary Cancer Laboratory, Hospital Universitario 12 de Octubre

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

BA1+BP4+BP6 -

Hereditary diffuse gastric adenocarcinoma

Benign:1

Oct 15, 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. -

Patterned macular dystrophy 2

Benign:1

Nov 13, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

3.7

(source)

DANN

Benign

0.62

PhyloP100

-0.68

PromoterAI

-0.045

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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