Variant 5-138754059-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2513 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA1	NM_001903.5 linkuse as main transcript	c.-3+549A>C		intron_variant		ENST00000302763.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA1	ENST00000302763.12 linkuse as main transcript	c.-3+549A>C		intron_variant		1	NM_001903.5	P1	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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0231

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0165

AC:

2513

AN:

152164

Hom.:

Cov.:

AF XY:

0.0163

AC XY:

1209

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00474

Gnomad4 AMR

AF:

0.00850

Gnomad4 ASJ

AF:

0.0256

Gnomad4 EAS

AF:

0.00136

Gnomad4 SAS

AF:

0.0164

Gnomad4 FIN

AF:

0.0268

Gnomad4 NFE

AF:

0.0249

Gnomad4 OTH

AF:

0.0156

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

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hereditary cancer-predisposing syndrome

Benign:1

Likely benign, no assertion criteria provided

clinical testing

University of Washington Department of Laboratory Medicine, University of Washington

Dec 01, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.7

DANN

Benign

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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