chr11-99845159-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_014361.4(CNTN5):c.474T>G(p.Ile158Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00768 in 1,613,768 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0079 ( 85 hom. )

Consequence

CNTN5
NM_014361.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.168

Publications

11 publications found

Variant links:

Genes affected

CNTN5 (HGNC:2175): (contactin 5) The protein encoded by this gene is a member of the immunoglobulin superfamily, and contactin family, which mediate cell surface interactions during nervous system development. This protein is a glycosylphosphatidylinositol (GPI)-anchored neuronal membrane protein that functions as a cell adhesion molecule. It may play a role in the formation of axon connections in the developing nervous system. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

CNTN5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013951659).

BP6

Variant 11-99845159-T-G is Benign according to our data. Variant chr11-99845159-T-G is described in ClinVar as [Benign]. Clinvar id is 720168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN5	NM_014361.4 link	c.474T>G	p.Ile158Met	missense_variant	Exon 6 of 25	ENST00000524871.6	NP_055176.1	O94779-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN5	ENST00000524871.6 link	c.474T>G	p.Ile158Met	missense_variant	Exon 6 of 25	1	NM_014361.4	ENSP00000435637.1		O94779-1

Frequencies

GnomAD3 genomes

AF:

0.00514

AC:

782

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00184

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.00197

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00434

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00881

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00539

AC:

1344

AN:

249232

AF XY:

0.00567

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.00348

Gnomad EAS exome

AF:

0.0000556

Gnomad FIN exome

AF:

0.00557

Gnomad NFE exome

AF:

0.00914

Gnomad OTH exome

AF:

0.00611

GnomAD4 exome

AF:

0.00795

AC:

11616

AN:

1461576

Hom.:

Cov.:

AF XY:

0.00757

AC XY:

5504

AN XY:

727072

show subpopulations

African (AFR)

AF:

0.00114

AC:

AN:

33478

American (AMR)

AF:

0.00105

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00318

AC:

AN:

26128

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39670

South Asian (SAS)

AF:

0.00132

AC:

114

AN:

86256

European-Finnish (FIN)

AF:

0.00676

AC:

361

AN:

53374

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00939

AC:

10443

AN:

1111818

Other (OTH)

AF:

0.00861

AC:

520

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

567

1134

1702

2269

2836

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00514

AC:

782

AN:

152192

Hom.:

Cov.:

AF XY:

0.00474

AC XY:

353

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.00183

AC:

AN:

41520

American (AMR)

AF:

0.00196

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00166

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00434

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00881

AC:

599

AN:

68014

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

118

157

196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00691

Hom.:

Bravo

AF:

0.00490

TwinsUK

AF:

0.0102

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00189

AC:

ESP6500EA

AF:

0.00694

AC:

ExAC

AF:

0.00564

AC:

681

EpiCase

AF:

0.00851

EpiControl

AF:

0.00818

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

CNTN5-related disorder

Benign:1

Jun 19, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

0.15

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

.;T;T;.;T;.

Eigen

Benign

0.18

Eigen_PC

Benign

0.090

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.86

D;.;D;D;D;D

M_CAP

Benign

0.039

MetaRNN

Benign

0.014

T;T;T;T;T;T

MetaSVM

Benign

-0.52

MutationAssessor

Benign

1.7

L;L;L;.;.;.

PhyloP100

-0.17

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.2

N;N;N;N;N;.

REVEL

Uncertain

0.38

Sift

Uncertain

0.0080

D;D;D;D;T;.

Sift4G

Uncertain

0.051

T;T;T;D;T;D

Polyphen

1.0

.;D;D;D;.;.

Vest4

0.41

MVP

0.72

MPC

0.049

ClinPred

0.047

GERP RS

0.25

Varity_R

0.23

gMVP

0.58

Mutation Taster

=93/7

polymorphism

(source)

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

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chr11-99845159-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over