Variant 5-138753726-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001903.5(CTNNA1):c.-3+216G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00595 in 317,062 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.011 ( 27 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 3 hom. )

Consequence

CTNNA1
NM_001903.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.330

Variant links:

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 links:

CTNNA1-AS1 (HGNC:):

CTNNA1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 5-138753726-G-A is Benign according to our data. Variant chr5-138753726-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1186093.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.011 (1678/152076) while in subpopulation AFR AF= 0.0384 (1595/41514). AF 95% confidence interval is 0.0369. There are 27 homozygotes in gnomad4. There are 795 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd at 1668 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA1	NM_001903.5 linkuse as main transcript	c.-3+216G>A		intron_variant		ENST00000302763.12
CTNNA1-AS1	NR_134244.1 linkuse as main transcript	n.199C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA1	ENST00000302763.12 linkuse as main transcript	c.-3+216G>A		intron_variant		1	NM_001903.5	P1	P35221-1

Frequencies

GnomAD3 genomes

AF:

0.0110

AC:

1668

AN:

151966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0383

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00669

GnomAD4 exome

AF:

0.00125

AC:

207

AN:

164986

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

AN XY:

84344

show subpopulations

Gnomad4 AFR exome

AF:

0.0347

Gnomad4 AMR exome

AF:

0.00192

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000851

Gnomad4 OTH exome

AF:

0.00368

GnomAD4 genome

AF:

0.0110

AC:

1678

AN:

152076

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

795

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0384

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00902

Hom.:

Bravo

AF:

0.0121

Asia WGS

AF:

0.00145

AC:

AN:

3468

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

Cadd

Benign

5.7

Dann

Benign

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over