5-138753541-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_001903.5(CTNNA1):c.-3+31G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00483 in 375,156 control chromosomes in the GnomAD database, including 27 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 0.0051 (14 hom., cov: 32)
  • Exomes 𝑓: 0.0046 (13 hom.)
• Consequence: CTNNA1 NM_001903.5 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0110

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:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 5-138753541-G-C is Benign according to our data. Variant chr5-138753541-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 223743.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00511 (773/151362) while in subpopulation AMR AF= 0.0295 (449/15224). AF 95% confidence interval is 0.0272. There are 14 homozygotes in gnomad4. There are 385 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 773 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA1	NM_001903.5	c.-3+31G>C		intron_variant		ENST00000302763.12
CTNNA1-AS1	NR_134244.1	n.384C>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA1	ENST00000302763.12	c.-3+31G>C		intron_variant		1	NM_001903.5	P1

Frequencies

GnomAD3 genomes AF: 0.00511 AC: 773 AN: 151254 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.000946

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0295

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00326

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00346

Gnomad OTH AF: 0.00433

GnomAD4 exome AF: 0.00464 AC: 1039 AN: 223794 Hom.: 13 Cov.: 0 AF XY: 0.00448 AC XY: 511 AN XY: 114088

Gnomad4 AFR exome AF: 0.00164

Gnomad4 AMR exome AF: 0.0478

Gnomad4 ASJ exome AF: 0.000126

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00139

Gnomad4 FIN exome AF: 0.00493

Gnomad4 NFE exome AF: 0.00377

Gnomad4 OTH exome AF: 0.00455

GnomAD4 genome AF: 0.00511 AC: 773 AN: 151362 Hom.: 14 Cov.: 32 AF XY: 0.00520 AC XY: 385 AN XY: 73990

Gnomad4 AFR AF: 0.000943

Gnomad4 AMR AF: 0.0295

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00326

Gnomad4 NFE AF: 0.00346

Gnomad4 OTH AF: 0.00428

Alfa AF: 0.00635 Hom.: 2

Bravo AF: 0.00855

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Hereditary cancer-predisposing syndrome Benign:1

Likely benign, no assertion criteria provided

clinical testing

University of Washington Department of Laboratory Medicine, University of Washington

Dec 01, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	6.9
Dann	Benign	0.75
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

Publications

LitVar

Other links and lift over

dbSNP: rs529217936; hg19: chr5-138089230;