rs6596456

Positions:

• chr5-138831808-A-G
• chr5-138831808-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000302763.12(CTNNA1):​c.1062+4090A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 152,062 control chromosomes in the GnomAD database, including 31,478 homozygotes. 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 0.63 (31478 hom., cov: 32)
• Consequence: CTNNA1 ENST00000302763.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA1	NM_001903.5	c.1062+4090A>G		intron_variant		ENST00000302763.12	NP_001894.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA1	ENST00000302763.12	c.1062+4090A>G		intron_variant		1	NM_001903.5	ENSP00000304669	P1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95865 AN: 151944 Hom.: 31457 Cov.: 32

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.671

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.631 AC: 95907 AN: 152062 Hom.: 31478 Cov.: 32 AF XY: 0.635 AC XY: 47158 AN XY: 74312

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.891

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.676

Alfa AF: 0.693 Hom.: 73966

Bravo AF: 0.626

Asia WGS AF: 0.784 AC: 2727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.0
DANN	Benign	0.78

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

Other links and lift over

dbSNP: rs6596456; hg19: chr5-138167497;