chr5-138824525-T-C

Position:

chr5-138824525-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001903.5(CTNNA1):c.589-5T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 1,612,304 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 20 hom. )

Consequence

CTNNA1
NM_001903.5 splice_region, intron

Scores

Splicing: ADA: 0.003529

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.46

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 (HGNC:):

CTNNA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 5-138824525-T-C is Benign according to our data. Variant chr5-138824525-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 239066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-138824525-T-C is described in Lovd as [Benign]. Variant chr5-138824525-T-C is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 294 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA1	NM_001903.5 linkuse as main transcript	c.589-5T>C		splice_region_variant, intron_variant		ENST00000302763.12	NP_001894.2	P35221-1A0A384MDY0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA1	ENST00000302763.12 linkuse as main transcript	c.589-5T>C		splice_region_variant, intron_variant		1	NM_001903.5	ENSP00000304669.7		P35221-1

Frequencies

GnomAD3 genomes

AF:

0.00193

AC:

294

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00357

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00179

AC:

449

AN:

250726

Hom.:

AF XY:

0.00182

AC XY:

247

AN XY:

135516

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00139

Gnomad NFE exome

AF:

0.00303

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00315

AC:

4595

AN:

1459978

Hom.:

Cov.:

AF XY:

0.00305

AC XY:

2215

AN XY:

725910

show subpopulations

Gnomad4 AFR exome

AF:

0.000509

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.00123

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00122

Gnomad4 NFE exome

AF:

0.00388

Gnomad4 OTH exome

AF:

0.00199

GnomAD4 genome

AF:

0.00193

AC:

294

AN:

152326

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

132

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00357

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00300

Hom.:

Bravo

AF:

0.00192

EpiCase

AF:

0.00398

EpiControl

AF:

0.00267

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	CTNNA1: BP4, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jul 06, 2021	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

CTNNA1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 19, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Hereditary cancer-predisposing syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 11, 2018

This alteration is classified as likely 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

-0.72

CADD

Benign

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0035

dbscSNV1_RF

Benign

0.022

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