5-138753397-G-C

Variant names:

• chr5-138753397-G-C
• rs62384262
• ENST00000523912.5:c.-3+226G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000523912.5(CTNNA1):​c.-3+226G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.000026 (0 hom., cov: 16)
  • Exomes 𝑓: 0.000046 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTNNA1 ENST00000523912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.534
• Publications: 3 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BS2: High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA1	NM_001903.5	c.-116G>C		upstream_gene_variant		ENST00000302763.12	NP_001894.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA1	ENST00000302763.12	c.-116G>C		upstream_gene_variant		1	NM_001903.5	ENSP00000304669.7

Frequencies

GnomAD3 genomes AF: 0.0000256 AC: 3 AN: 117348 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.0000309

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000809

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000187

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000459 AC: 9 AN: 196038 Hom.: 0 Cov.: 0 AF XY: 0.0000399 AC XY: 4 AN XY: 100326

African (AFR) AF: 0.00 AC: 0 AN: 5198

American (AMR) AF: 0.00 AC: 0 AN: 5736

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6778

East Asian (EAS) AF: 0.0000535 AC: 1 AN: 18688

South Asian (SAS) AF: 0.00 AC: 0 AN: 2608

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1022

European-Non Finnish (NFE) AF: 0.0000560 AC: 7 AN: 124990

Other (OTH) AF: 0.0000805 AC: 1 AN: 12424

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000256 AC: 3 AN: 117414 Hom.: 0 Cov.: 16 AF XY: 0.0000352 AC XY: 2 AN XY: 56884

African (AFR) AF: 0.0000308 AC: 1 AN: 32440

American (AMR) AF: 0.0000809 AC: 1 AN: 12364

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2916

East Asian (EAS) AF: 0.00 AC: 0 AN: 3452

South Asian (SAS) AF: 0.00 AC: 0 AN: 3458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6840

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 214

European-Non Finnish (NFE) AF: 0.0000187 AC: 1 AN: 53556

Other (OTH) AF: 0.00 AC: 0 AN: 1624

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	16
DANN	Benign	0.63
PhyloP100		0.53
PromoterAI		0.030	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs62384262; hg19: chr5-138089086;