5-138932622-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001903.5(CTNNA1):ā€‹c.2343A>Gā€‹(p.Gln781=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00188 in 1,614,162 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0092 ( 21 hom., cov: 32)
Exomes š‘“: 0.0011 ( 35 hom. )

Consequence

CTNNA1
NM_001903.5 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: 3.69
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
Variant 5-138932622-A-G is Benign according to our data. Variant chr5-138932622-A-G is described in ClinVar as [Benign]. Clinvar id is 239064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-138932622-A-G is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00921 (1402/152276) while in subpopulation AFR AF= 0.0316 (1315/41556). AF 95% confidence interval is 0.0302. There are 21 homozygotes in gnomad4. There are 640 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1402 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CTNNA1NM_001903.5 linkuse as main transcriptc.2343A>G p.Gln781= synonymous_variant 17/18 ENST00000302763.12 NP_001894.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CTNNA1ENST00000302763.12 linkuse as main transcriptc.2343A>G p.Gln781= synonymous_variant 17/181 NM_001903.5 ENSP00000304669 P1P35221-1

Frequencies

GnomAD3 genomes
AF:
0.00921
AC:
1401
AN:
152158
Hom.:
21
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0317
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00308
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00166
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000235
Gnomad OTH
AF:
0.00764
GnomAD3 exomes
AF:
0.00268
AC:
674
AN:
251380
Hom.:
15
AF XY:
0.00201
AC XY:
273
AN XY:
135868
show subpopulations
Gnomad AFR exome
AF:
0.0345
Gnomad AMR exome
AF:
0.00179
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000947
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000123
Gnomad OTH exome
AF:
0.00147
GnomAD4 exome
AF:
0.00111
AC:
1626
AN:
1461886
Hom.:
35
Cov.:
32
AF XY:
0.000994
AC XY:
723
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0347
Gnomad4 AMR exome
AF:
0.00199
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00110
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000122
Gnomad4 OTH exome
AF:
0.00232
GnomAD4 genome
AF:
0.00921
AC:
1402
AN:
152276
Hom.:
21
Cov.:
32
AF XY:
0.00860
AC XY:
640
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.0316
Gnomad4 AMR
AF:
0.00307
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00166
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000235
Gnomad4 OTH
AF:
0.00756
Alfa
AF:
0.00536
Hom.:
9
Bravo
AF:
0.0107
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000296

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
Benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, Amsterdam University Medical Center-- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitterclinical testingAmbry GeneticsMay 09, 2019This 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
CADD
Benign
6.2
DANN
Benign
0.64
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8

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.

Other links and lift over

dbSNP: rs75050399; hg19: chr5-138268311; COSMIC: COSV104406637; COSMIC: COSV104406637; API