5-138756008-T-G

Position:

• chr5-138756008-T-G

Variant summary

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

The NM_001903.5(CTNNA1):​c.-3+2498T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0597 in 149,184 control chromosomes in the GnomAD database, including 361 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 0.060 (361 hom., cov: 25)
• Consequence: CTNNA1 NM_001903.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.297

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA1	NM_001903.5	c.-3+2498T>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.-3+2498T>G		intron_variant		1	NM_001903.5	ENSP00000304669.7

Frequencies

GnomAD3 genomes AF: 0.0597 AC: 8902 AN: 149066 Hom.: 360 Cov.: 25

Gnomad AFR AF: 0.0191

Gnomad AMI AF: 0.00332

Gnomad AMR AF: 0.0799

Gnomad ASJ AF: 0.0902

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0891

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.0639

Gnomad OTH AF: 0.0814

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

GnomAD4 genome AF: 0.0597 AC: 8902 AN: 149184 Hom.: 361 Cov.: 25 AF XY: 0.0625 AC XY: 4544 AN XY: 72666

Gnomad4 AFR AF: 0.0192

Gnomad4 AMR AF: 0.0797

Gnomad4 ASJ AF: 0.0902

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.0891

Gnomad4 NFE AF: 0.0638

Gnomad4 OTH AF: 0.0829

Alfa AF: 0.0626 Hom.: 261

Bravo AF: 0.0588

Asia WGS AF: 0.154 AC: 534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.47

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: rs12653845; hg19: chr5-138091697;