Genetic Variant CTNNA1:c.-3+226G>A (chr5-138753397-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000522227.5(CTNNA1):c.-2-28526G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.60 ( 21305 hom., cov: 16)

Exomes 𝑓: 0.71 ( 51106 hom. )

Consequence

CTNNA1
ENST00000522227.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.534

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:

CTNNA1-AS1 (HGNC:55535): (CTNNA1 antisense RNA 1)

CTNNA1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 5-138753397-G-A is Benign according to our data. Variant chr5-138753397-G-A is described in ClinVar as [Benign]. Clinvar id is 1292329.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA1	NM_001903.5 link	c.-116G>A		upstream_gene_variant		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.-116G>A		upstream_gene_variant		1	NM_001903.5	ENSP00000304669.7		P35221-1

Frequencies

GnomAD3 genomes

AF:

0.599

AC:

70089

AN:

117018

Hom.:

21299

Cov.:

show subpopulations

Gnomad AFR

AF:

0.434

Gnomad AMI

AF:

0.615

Gnomad AMR

AF:

0.705

Gnomad ASJ

AF:

0.615

Gnomad EAS

AF:

0.913

Gnomad SAS

AF:

0.660

Gnomad FIN

AF:

0.656

Gnomad MID

AF:

0.643

Gnomad NFE

AF:

0.640

Gnomad OTH

AF:

0.641

GnomAD4 exome

AF:

0.715

AC:

140052

AN:

195930

Hom.:

51106

Cov.:

AF XY:

0.713

AC XY:

71459

AN XY:

100278

show subpopulations

Gnomad4 AFR exome

AF:

0.499

AC:

2592

AN:

5192

Gnomad4 AMR exome

AF:

0.742

AC:

4255

AN:

5732

Gnomad4 ASJ exome

AF:

0.672

AC:

4555

AN:

6778

Gnomad4 EAS exome

AF:

0.930

AC:

17380

AN:

18684

Gnomad4 SAS exome

AF:

0.701

AC:

1826

AN:

2606

Gnomad4 FIN exome

AF:

0.690

AC:

12828

AN:

18578

Gnomad4 NFE exome

AF:

0.698

AC:

87184

AN:

124922

Gnomad4 Remaining exome

AF:

0.700

AC:

8694

AN:

12416

Heterozygous variant carriers

1770

3541

5311

7082

8852

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

334

668

1002

1336

1670

<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:

0.599

AC:

70112

AN:

117084

Hom.:

21305

Cov.:

AF XY:

0.605

AC XY:

34302

AN XY:

56710

show subpopulations

Gnomad4 AFR

AF:

0.434

AC:

0.433853

AN:

0.433853

Gnomad4 AMR

AF:

0.706

AC:

0.705644

AN:

0.705644

Gnomad4 ASJ

AF:

0.615

AC:

0.614512

AN:

0.614512

Gnomad4 EAS

AF:

0.913

AC:

0.913144

AN:

0.913144

Gnomad4 SAS

AF:

0.662

AC:

0.662115

AN:

0.662115

Gnomad4 FIN

AF:

0.656

AC:

0.655718

AN:

0.655718

Gnomad4 NFE

AF:

0.640

AC:

0.639828

AN:

0.639828

Gnomad4 OTH

AF:

0.647

AC:

0.646732

AN:

0.646732

Heterozygous variant carriers

1172

2344

3515

4687

5859

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<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:

0.00

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 15, 2019

GeneDx

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

-0.69

CADD

Benign

DANN

Benign

0.91

Mutation Taster

=100/0

polymorphism (auto)

Splicing

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