rs4835711

chr5-138887191-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001903.5(CTNNA1):c.1144-299G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 152,124 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.020 (38 hom., cov: 32)
• Consequence: CTNNA1 NM_001903.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.432

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 5-138887191-G-A is Benign according to our data. Variant chr5-138887191-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 223698.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0196 (2977/152124) while in subpopulation AMR AF= 0.0298 (455/15260). AF 95% confidence interval is 0.0276. There are 38 homozygotes in gnomad4. There are 1416 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 2977 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA1	NM_001903.5	c.1144-299G>A		intron_variant		ENST00000302763.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA1	ENST00000302763.12	c.1144-299G>A		intron_variant		1	NM_001903.5	P1

Frequencies

GnomAD3 genomes AF: 0.0196 AC: 2977 AN: 152006 Hom.: 38 Cov.: 32

Gnomad AFR AF: 0.00463

Gnomad AMI AF: 0.0673

Gnomad AMR AF: 0.0298

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0229

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0273

Gnomad OTH AF: 0.0235

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

GnomAD4 genome AF: 0.0196 AC: 2977 AN: 152124 Hom.: 38 Cov.: 32 AF XY: 0.0190 AC XY: 1416 AN XY: 74368

Gnomad4 AFR AF: 0.00462

Gnomad4 AMR AF: 0.0298

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.0229

Gnomad4 NFE AF: 0.0273

Gnomad4 OTH AF: 0.0233

Alfa AF: 0.0186 Hom.: 4

Bravo AF: 0.0199

Asia WGS AF: 0.00260 AC: 9 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	8.7
Dann	Benign	0.85

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: rs4835711; hg19: chr5-138222880;