rs288023

chr5-138888359-A-G

Variant summary

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

The NM_001903.5(CTNNA1):c.1296+717A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,076 control chromosomes in the GnomAD database, including 8,035 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 0.32 (8035 hom., cov: 32)
• Consequence: CTNNA1 NM_001903.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202

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=-0.89).
• 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	UniProt
CTNNA1	NM_001903.5	c.1296+717A>G		intron_variant		ENST00000302763.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA1	ENST00000302763.12	c.1296+717A>G		intron_variant		1	NM_001903.5	P1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48619 AN: 151958 Hom.: 8018 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.0683

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.320 AC: 48670 AN: 152076 Hom.: 8035 Cov.: 32 AF XY: 0.316 AC XY: 23502 AN XY: 74344

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.0679

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.287

Alfa AF: 0.328 Hom.: 1024

Bravo AF: 0.318

Asia WGS AF: 0.190 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.8
Dann	Benign	0.44

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: rs288023; hg19: chr5-138224048; COSMIC: COSV57071661; COSMIC: COSV57071661;