5-138788305-T-G

Variant names:

• chr5-138788305-T-G
• rs700629
• NM_001903.5:c.301+4933T>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.301+4933T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 152,034 control chromosomes in the GnomAD database, including 32,222 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 0.64 (32222 hom., cov: 31)
• Consequence: CTNNA1 NM_001903.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 5 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• 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 = 0.869 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.301+4933T>G		intron	N/A	NP_001894.2	A0A384MDY0
	CTNNA1	NM_001323982.2		c.301+4933T>G		intron	N/A	NP_001310911.1	P35221-1
	CTNNA1	NM_001323983.1		c.301+4933T>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.301+4933T>G		intron	N/A	ENSP00000304669.7	P35221-1
	CTNNA1	ENST00000518825.5	TSL:1	c.301+4933T>G		intron	N/A	ENSP00000427821.1	G3XAM7
	CTNNA1	ENST00000965845.1		c.301+4933T>G		intron	N/A	ENSP00000635904.1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97589 AN: 151916 Hom.: 32201 Cov.: 31

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.679

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

GnomAD4 genome AF: 0.642 AC: 97637 AN: 152034 Hom.: 32222 Cov.: 31 AF XY: 0.646 AC XY: 48051 AN XY: 74336

African (AFR) AF: 0.467 AC: 19360 AN: 41444

American (AMR) AF: 0.734 AC: 11203 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2296 AN: 3472

East Asian (EAS) AF: 0.890 AC: 4596 AN: 5164

South Asian (SAS) AF: 0.702 AC: 3381 AN: 4814

European-Finnish (FIN) AF: 0.705 AC: 7443 AN: 10560

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 47070 AN: 67996

Other (OTH) AF: 0.684 AC: 1445 AN: 2114

Alfa AF: 0.622 Hom.: 4106

Bravo AF: 0.640

Asia WGS AF: 0.788 AC: 2741 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	6.4
DANN	Benign	0.42
PhyloP100		1.2
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: rs700629; hg19: chr5-138123994;