5-138788305-T-G

Position:

• chr5-138788305-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA1	NM_001903.5	c.301+4933T>G		intron_variant		ENST00000302763.12	NP_001894.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA1	ENST00000302763.12	c.301+4933T>G		intron_variant		1	NM_001903.5	ENSP00000304669.7

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

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.734

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.890

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.705

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.684

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.4
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs700629; hg19: chr5-138123994;