5-138781152-C-G

Variant names:

• chr5-138781152-C-G
• rs6893685
• NM_001903.5:c.-2-771C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001903.5(CTNNA1):​c.-2-771C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 152,232 control chromosomes in the GnomAD database, including 136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: 𝑓 0.023 (136 hom., cov: 32)
• Consequence: CTNNA1 NM_001903.5 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.203
• Publications: 0 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 5-138781152-C-G is Benign according to our data. Variant chr5-138781152-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 223773.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA1	NM_001903.5	c.-2-771C>G		intron_variant	Intron 1 of 17	ENST00000302763.12	NP_001894.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA1	ENST00000302763.12	c.-2-771C>G		intron_variant	Intron 1 of 17	1	NM_001903.5	ENSP00000304669.7

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3491 AN: 152114 Hom.: 137 Cov.: 32

Gnomad AFR AF: 0.0810

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00635

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0105

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

GnomAD4 genome AF: 0.0229 AC: 3488 AN: 152232 Hom.: 136 Cov.: 32 AF XY: 0.0225 AC XY: 1674 AN XY: 74428

African (AFR) AF: 0.0807 AC: 3353 AN: 41546

American (AMR) AF: 0.00634 AC: 97 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68012

Other (OTH) AF: 0.0104 AC: 22 AN: 2116

Alfa AF: 0.000359 Hom.: 0

Bravo AF: 0.0261

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Hereditary cancer-predisposing syndrome Benign:1

Dec 01, 2015

University of Washington Department of Laboratory Medicine, University of Washington

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.0
DANN	Benign	0.82
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: rs6893685; hg19: chr5-138116841;