rs6596456

Variant names:

• chr5-138831808-A-G
• rs6596456
• NM_001903.5:c.1062+4090A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-138831808-A-G
• chr5-138831808-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001903.5(CTNNA1):​c.1062+4090A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 152,062 control chromosomes in the GnomAD database, including 31,478 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 0.63 (31478 hom., cov: 32)
• Consequence: CTNNA1 NM_001903.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 10 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• patterned macular dystrophy

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

  Inheritance: Unknown 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 (EAS) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001903.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA1	NM_001903.5	MANE Select	c.1062+4090A>G		intron	N/A	NP_001894.2	A0A384MDY0
	CTNNA1	NM_001323982.2		c.1062+4090A>G		intron	N/A	NP_001310911.1	P35221-1
	CTNNA1	NM_001323983.1		c.1062+4090A>G		intron	N/A	NP_001310912.1	A0A384MDY0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA1	ENST00000302763.12	TSL:1 MANE Select	c.1062+4090A>G		intron	N/A	ENSP00000304669.7	P35221-1
	CTNNA1	ENST00000518825.5	TSL:1	c.1062+4090A>G		intron	N/A	ENSP00000427821.1	G3XAM7
	CTNNA1	ENST00000965845.1		c.1062+4090A>G		intron	N/A	ENSP00000635904.1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95865 AN: 151944 Hom.: 31457 Cov.: 32

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.631 AC: 95907 AN: 152062 Hom.: 31478 Cov.: 32 AF XY: 0.635 AC XY: 47158 AN XY: 74312

African (AFR) AF: 0.428 AC: 17735 AN: 41464

American (AMR) AF: 0.730 AC: 11135 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2293 AN: 3470

East Asian (EAS) AF: 0.891 AC: 4612 AN: 5174

South Asian (SAS) AF: 0.700 AC: 3376 AN: 4826

European-Finnish (FIN) AF: 0.704 AC: 7435 AN: 10568

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 47071 AN: 67980

Other (OTH) AF: 0.676 AC: 1427 AN: 2112

Alfa AF: 0.676 Hom.: 111836

Bravo AF: 0.626

Asia WGS AF: 0.784 AC: 2727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.0
DANN	Benign	0.78
PhyloP100		0.011
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6596456; hg19: chr5-138167497;