rs3763016

Positions:

• chr5-138935043-C-G
• chr5-138935043-C-T

Variant summary

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

The variant allele was found at a frequency of 0.349 in 152,142 control chromosomes in the GnomAD database, including 10,057 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 0.35 (10057 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257

Genes affected

(HGNC:):

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA1	NM_001903.5	c.*954C>G		downstream_gene_variant		ENST00000302763.12	NP_001894.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA1	ENST00000302763.12	c.*954C>G		downstream_gene_variant		1	NM_001903.5	ENSP00000304669.7
CTNNA1	ENST00000540387.5	c.*954C>G		downstream_gene_variant		1		ENSP00000438476.1
CTNNA1	ENST00000627109.2	c.*1220C>G		downstream_gene_variant		5		ENSP00000486200.1
CTNNA1	ENST00000522792.1	n.*10C>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52987 AN: 152020 Hom.: 10035 Cov.: 33

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.0486

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.312

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.349 AC: 53050 AN: 152140 Hom.: 10057 Cov.: 33 AF XY: 0.344 AC XY: 25576 AN XY: 74364

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.0485

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.309

Alfa AF: 0.226 Hom.: 536

Bravo AF: 0.351

Asia WGS AF: 0.162 AC: 563 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	4.2
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3763016; hg19: chr5-138270732; COSMIC: COSV57072099;