5-138644787-C-T

Variant names:

• chr5-138644787-C-T
• rs3849047
• ENST00000522227.5:c.-162+33698C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• CTNNA1-related diffuse gastric and lobular breast cancer syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• patterned macular dystrophy 2

  Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• patterned macular dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary nonpolyposis colon cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA1	ENST00000522227.5	c.-162+33698C>T		intron_variant	Intron 1 of 4	3		ENSP00000429636.1
CTNNA1	ENST00000517980.5	c.-220-8277C>T		intron_variant	Intron 1 of 5	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

African (AFR) AF: 0.210 AC: 8707 AN: 41486

American (AMR) AF: 0.249 AC: 3812 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1100 AN: 3464

East Asian (EAS) AF: 0.280 AC: 1447 AN: 5170

South Asian (SAS) AF: 0.375 AC: 1808 AN: 4824

European-Finnish (FIN) AF: 0.435 AC: 4592 AN: 10568

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23241 AN: 67956

Other (OTH) AF: 0.305 AC: 642 AN: 2108

Alfa AF: 0.321 Hom.: 9791

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
PhyloP100		-0.80

Splicing

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

Other links and lift over

dbSNP: rs3849047; hg19: chr5-137980476;