5-138753541-G-A

Variant names:

• chr5-138753541-G-A
• rs529217936
• NM_001903.5:c.-3+31G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001903.5(CTNNA1):​c.-3+31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000447 in 223,800 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000045 (0 hom.)
• Consequence: CTNNA1 NM_001903.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• 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-AS1 (HGNC:55535): (CTNNA1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).

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.-3+31G>A		intron	N/A	NP_001894.2	A0A384MDY0
	CTNNA1	NM_001323982.2		c.-473+31G>A		intron	N/A	NP_001310911.1	P35221-1
	CTNNA1	NM_001323984.2		c.-21+31G>A		intron	N/A	NP_001310913.1	P35221-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA1	ENST00000302763.12	TSL:1 MANE Select	c.-3+31G>A		intron	N/A	ENSP00000304669.7	P35221-1
	CTNNA1	ENST00000965845.1		c.-3+31G>A		intron	N/A	ENSP00000635904.1
	CTNNA1	ENST00000930310.1		c.-3+31G>A		intron	N/A	ENSP00000600369.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000447 AC: 1 AN: 223800 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 114090

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 6102

American (AMR) AF: 0.00 AC: 0 AN: 6630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7960

East Asian (EAS) AF: 0.00 AC: 0 AN: 21174

South Asian (SAS) AF: 0.00 AC: 0 AN: 2882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1154

European-Non Finnish (NFE) AF: 0.00000699 AC: 1 AN: 143140

Other (OTH) AF: 0.00 AC: 0 AN: 14492

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.8
DANN	Uncertain	0.98
PhyloP100		0.011
PromoterAI		0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs529217936; hg19: chr5-138089230;