chr5-138888359-A-G

Variant names:

• chr5-138888359-A-G
• rs288023
• NM_001903.5:c.1296+717A>G

Variant summary

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

The NM_001903.5(CTNNA1):​c.1296+717A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,076 control chromosomes in the GnomAD database, including 8,035 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 0.32 (8035 hom., cov: 32)
• Consequence: CTNNA1 NM_001903.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.402 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.1296+717A>G		intron	N/A	NP_001894.2
	CTNNA1	NM_001323982.2		c.1296+717A>G		intron	N/A	NP_001310911.1
	CTNNA1	NM_001323983.1		c.1296+717A>G		intron	N/A	NP_001310912.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA1	ENST00000302763.12	TSL:1 MANE Select	c.1296+717A>G		intron	N/A	ENSP00000304669.7
	CTNNA1	ENST00000518825.5	TSL:1	c.1296+717A>G		intron	N/A	ENSP00000427821.1
	CTNNA1	ENST00000540387.5	TSL:1	c.186+717A>G		intron	N/A	ENSP00000438476.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48619 AN: 151958 Hom.: 8018 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.0683

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.320 AC: 48670 AN: 152076 Hom.: 8035 Cov.: 32 AF XY: 0.316 AC XY: 23502 AN XY: 74344

African (AFR) AF: 0.408 AC: 16887 AN: 41426

American (AMR) AF: 0.252 AC: 3859 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1183 AN: 3472

East Asian (EAS) AF: 0.0679 AC: 352 AN: 5182

South Asian (SAS) AF: 0.290 AC: 1396 AN: 4820

European-Finnish (FIN) AF: 0.294 AC: 3108 AN: 10566

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

European-Non Finnish (NFE) AF: 0.307 AC: 20899 AN: 68002

Other (OTH) AF: 0.287 AC: 605 AN: 2110

Alfa AF: 0.331 Hom.: 1084

Bravo AF: 0.318

Asia WGS AF: 0.190 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.44
PhyloP100		0.20
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: rs288023; hg19: chr5-138224048; COSMIC: COSV57071661; COSMIC: COSV57071661;