11-57794071-A-G

Position:

chr11-57794071-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001085458.2(CTNND1):c.257A>G(p.Asn86Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,613,996 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. N86N) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 4 hom. )

Consequence

CTNND1
NM_001085458.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.97

Variant links:

Genes affected

CTNND1 (HGNC:2515): (catenin delta 1) This gene encodes a member of the Armadillo protein family, which function in adhesion between cells and signal transduction. Multiple translation initiation codons and alternative splicing result in many different isoforms being translated. Not all of the full-length natures of the described transcript variants have been determined. Read-through transcription also exists between this gene and the neighboring upstream thioredoxin-related transmembrane protein 2 (TMX2) gene. [provided by RefSeq, Dec 2010]

CTNND1 links:

TMX2-CTNND1 (HGNC:):

TMX2-CTNND1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007977247).

BP6

Variant 11-57794071-A-G is Benign according to our data. Variant chr11-57794071-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 722491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-57794071-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00102 (155/152318) while in subpopulation AMR AF= 0.00268 (41/15304). AF 95% confidence interval is 0.00203. There are 0 homozygotes in gnomad4. There are 70 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 155 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNND1	NM_001085458.2 linkuse as main transcript	c.257A>G	p.Asn86Ser	missense_variant	4/21	ENST00000399050.10	NP_001078927.1
TMX2-CTNND1	NR_037646.1 linkuse as main transcript	n.816A>G		non_coding_transcript_exon_variant	5/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNND1	ENST00000399050.10 linkuse as main transcript	c.257A>G	p.Asn86Ser	missense_variant	4/21	1	NM_001085458.2	ENSP00000382004		O60716-1

Frequencies

GnomAD3 genomes

AF:

0.00102

AC:

155

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00122

AC:

301

AN:

246852

Hom.:

AF XY:

0.00119

AC XY:

160

AN XY:

134144

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.000666

Gnomad ASJ exome

AF:

0.0129

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.00120

Gnomad OTH exome

AF:

0.000993

GnomAD4 exome

AF:

0.00109

AC:

1586

AN:

1461678

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

791

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000917

Gnomad4 ASJ exome

AF:

0.0140

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.000941

Gnomad4 OTH exome

AF:

0.00157

GnomAD4 genome

AF:

0.00102

AC:

155

AN:

152318

Hom.:

Cov.:

AF XY:

0.000940

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00144

Hom.:

Bravo

AF:

0.00127

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000541

AC:

ESP6500EA

AF:

0.00147

AC:

ExAC

AF:

0.00104

AC:

126

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.000652

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	CTNND1: BP4 -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

CTNND1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 09, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

.;T;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;T

Eigen

Benign

-0.099

Eigen_PC

Benign

0.034

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.91

.;D;D;.;D;D;D;.;.;.;D;D;D;D;D;D;D;D

M_CAP

Benign

0.029

MetaRNN

Benign

0.0080

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

0.76

N;.;N;.;N;N;N;N;.;.;.;N;.;.;.;.;N;.

MutationTaster

Benign

0.92

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.72

N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.072

Sift

Benign

0.036

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

Sift4G

Benign

0.43

T;T;T;D;T;T;T;T;D;D;D;T;D;D;D;D;T;T

Polyphen

0.011

B;B;P;.;P;.;P;B;.;.;.;B;.;.;D;.;.;.

Vest4

0.20

MVP

0.78

MPC

0.27

ClinPred

0.028

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.41

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