Genetic Variant CTNNA1:c.-3+549A>C (chr5-138754059-A-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001903.5(CTNNA1):c.-3+549A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 152,318 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.017 ( 25 hom., cov: 32)

Exomes 𝑓: 0.019 ( 0 hom. )

Consequence

CTNNA1
NM_001903.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.0500

Publications

0 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 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=-0.82).

BP6

Variant 5-138754059-A-C is Benign according to our data. Variant chr5-138754059-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 223774.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0165 (2513/152164) while in subpopulation NFE AF = 0.0249 (1693/67976). AF 95% confidence interval is 0.0239. There are 25 homozygotes in GnomAd4. There are 1209 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2513 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA1	NM_001903.5 link	c.-3+549A>C		intron_variant	Intron 1 of 17	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.-3+549A>C		intron_variant	Intron 1 of 17	1	NM_001903.5	ENSP00000304669.7		P35221-1

Frequencies

GnomAD3 genomes

AF:

0.0165

AC:

2511

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00476

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00857

Gnomad ASJ

AF:

0.0256

Gnomad EAS

AF:

0.00136

Gnomad SAS

AF:

0.0160

Gnomad FIN

AF:

0.0268

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0249

Gnomad OTH

AF:

0.0158

GnomAD4 exome

AF:

0.0195

AC:

AN:

154

Hom.:

Cov.:

AF XY:

0.0246

AC XY:

AN XY:

122

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0231

AC:

AN:

130

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0165

AC:

2513

AN:

152164

Hom.:

Cov.:

AF XY:

0.0163

AC XY:

1209

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.00474

AC:

197

AN:

41538

American (AMR)

AF:

0.00850

AC:

130

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0256

AC:

AN:

3470

East Asian (EAS)

AF:

0.00136

AC:

AN:

5146

South Asian (SAS)

AF:

0.0164

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.0268

AC:

284

AN:

10606

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0249

AC:

1693

AN:

67976

Other (OTH)

AF:

0.0156

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

130

260

389

519

649

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0195

Hom.:

Bravo

AF:

0.0152

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Hereditary cancer-predisposing syndrome

Benign:1

Dec 01, 2015

University of Washington Department of Laboratory Medicine, University of Washington

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.7

(source)

DANN

Benign

0.51

PhyloP100

-0.050

PromoterAI

0.0068

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism

(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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5-138754059-A-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over