Variant chr5-138930857-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The ENST00000302763.12(CTNNA1):c.2220G>A(p.Ser740=) 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
ENST00000302763.12 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.681

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 -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 id is 820919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-138930857-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
CTNNA1	NM_001903.5 linkuse as main transcript	c.2220G>A	p.Ser740=	synonymous_variant	16/18	ENST00000302763.12	NP_001894.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA1	ENST00000302763.12 linkuse as main transcript	c.2220G>A	p.Ser740=	synonymous_variant	16/18	1	NM_001903.5	ENSP00000304669	P1	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

GnomAD3 exomes

AF:

0.274

AC:

68952

AN:

251416

Hom.:

10445

AF XY:

0.273

AC XY:

37033

AN XY:

135894

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 SAS exome

AF:

0.259

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

Gnomad4 AFR exome

AF:

0.413

Gnomad4 AMR exome

AF:

0.268

Gnomad4 ASJ exome

AF:

0.328

Gnomad4 EAS exome

AF:

0.00927

Gnomad4 SAS exome

AF:

0.263

Gnomad4 FIN exome

AF:

0.304

Gnomad4 NFE exome

AF:

0.295

Gnomad4 OTH exome

AF:

0.282

GnomAD4 genome

AF:

0.314

AC:

47784

AN:

152036

Hom.:

7853

Cov.:

AF XY:

0.309

AC XY:

22995

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.407

Gnomad4 AMR

AF:

0.250

Gnomad4 ASJ

AF:

0.337

Gnomad4 EAS

AF:

0.00637

Gnomad4 SAS

AF:

0.236

Gnomad4 FIN

AF:

0.295

Gnomad4 NFE

AF:

0.304

Gnomad4 OTH

AF:

0.283

Alfa

AF:

0.298

Hom.:

8893

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:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -

Hereditary cancer-predisposing syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2018

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. -

Patterned macular dystrophy 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 30, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

3.7

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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