5-138753397-G-A

Variant names:

• chr5-138753397-G-A
• rs62384262
• ENST00000523912.5:c.-3+226G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000522227.5(CTNNA1):​c.-2-28526G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.60 (21305 hom., cov: 16)
  • Exomes 𝑓: 0.71 (51106 hom.)
• Consequence: CTNNA1 ENST00000522227.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.534
• 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-AS1 (HGNC:55535): (CTNNA1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 5-138753397-G-A is Benign according to our data. Variant chr5-138753397-G-A is described in ClinVar as [Benign]. Clinvar id is 1292329.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA1	NM_001903.5	c.-116G>A		upstream_gene_variant		ENST00000302763.12	NP_001894.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA1	ENST00000302763.12	c.-116G>A		upstream_gene_variant		1	NM_001903.5	ENSP00000304669.7

Frequencies

GnomAD3 genomes AF: 0.599 AC: 70089 AN: 117018 Hom.: 21299 Cov.: 16

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.643

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.641

GnomAD4 exome AF: 0.715 AC: 140052 AN: 195930 Hom.: 51106 Cov.: 0 AF XY: 0.713 AC XY: 71459 AN XY: 100278

African (AFR) AF: 0.499 AC: 2592 AN: 5192

American (AMR) AF: 0.742 AC: 4255 AN: 5732

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 4555 AN: 6778

East Asian (EAS) AF: 0.930 AC: 17380 AN: 18684

South Asian (SAS) AF: 0.701 AC: 1826 AN: 2606

European-Finnish (FIN) AF: 0.690 AC: 12828 AN: 18578

Middle Eastern (MID) AF: 0.722 AC: 738 AN: 1022

European-Non Finnish (NFE) AF: 0.698 AC: 87184 AN: 124922

Other (OTH) AF: 0.700 AC: 8694 AN: 12416

GnomAD4 genome AF: 0.599 AC: 70112 AN: 117084 Hom.: 21305 Cov.: 16 AF XY: 0.605 AC XY: 34302 AN XY: 56710

African (AFR) AF: 0.434 AC: 14036 AN: 32352

American (AMR) AF: 0.706 AC: 8702 AN: 12332

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 1787 AN: 2908

East Asian (EAS) AF: 0.913 AC: 3154 AN: 3454

South Asian (SAS) AF: 0.662 AC: 2279 AN: 3442

European-Finnish (FIN) AF: 0.656 AC: 4472 AN: 6820

Middle Eastern (MID) AF: 0.626 AC: 134 AN: 214

European-Non Finnish (NFE) AF: 0.640 AC: 34163 AN: 53394

Other (OTH) AF: 0.647 AC: 1049 AN: 1622

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 15, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	17
DANN	Benign	0.91
PhyloP100		0.53
PromoterAI		0.13	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs62384262; hg19: chr5-138089086; COSMIC: COSV57071175;