Genetic Variant CTNNA1:c.-3+226G>C (chr5-138753397-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000522227.5(CTNNA1):c.-2-28526G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 16)

Exomes 𝑓: 0.000046 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CTNNA1
ENST00000522227.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.534

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA1	NM_001903.5 link	c.-116G>C		upstream_gene_variant		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.-116G>C		upstream_gene_variant		1	NM_001903.5	ENSP00000304669.7		P35221-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

117348

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000309

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000809

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000187

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000459

AC:

AN:

196038

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

100326

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000535

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000560

Gnomad4 OTH exome

AF:

0.0000805

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000256

AC:

AN:

117414

Hom.:

Cov.:

AF XY:

0.0000352

AC XY:

AN XY:

56884

show subpopulations

Gnomad4 AFR

AF:

0.0000308

Gnomad4 AMR

AF:

0.0000809

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000187

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.63

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over