5-138644787-C-T

Position:

• chr5-138644787-C-T

Variant summary

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

The ENST00000522227.5(CTNNA1):​c.-162+33698C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,072 control chromosomes in the GnomAD database, including 7,268 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 0.30 (7268 hom., cov: 32)
• Consequence: CTNNA1 ENST00000522227.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.802

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 (SAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA1	ENST00000522227.5	c.-162+33698C>T		intron_variant		3		ENSP00000429636.1
CTNNA1	ENST00000517980.5	c.-220-8277C>T		intron_variant		4		ENSP00000428439.1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45849 AN: 151954 Hom.: 7276 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.301 AC: 45847 AN: 152072 Hom.: 7268 Cov.: 32 AF XY: 0.305 AC XY: 22681 AN XY: 74326

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.305

Alfa AF: 0.327 Hom.: 7678

Bravo AF: 0.283

Asia WGS AF: 0.322 AC: 1122 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	1.7
DANN	Benign	0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3849047; hg19: chr5-137980476;