12-40943633-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001843.4(CNTN1):c.1416C>T(p.Asn472Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 1,591,976 control chromosomes in the GnomAD database, including 305,935 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 29423 hom., cov: 32)

Exomes 𝑓: 0.62 ( 276512 hom. )

Consequence

CNTN1
NM_001843.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.557

Publications

23 publications found

Variant links:

Genes affected

CNTN1 (HGNC:2171): (contactin 1) The protein encoded by this gene is a member of the immunoglobulin superfamily. It 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. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

CNTN1 Gene-Disease associations (from GenCC):

Compton-North congenital myopathy
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

CNTN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 12-40943633-C-T is Benign according to our data. Variant chr12-40943633-C-T is described in ClinVar as [Benign]. Clinvar id is 128791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.557 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN1	NM_001843.4 link	c.1416C>T	p.Asn472Asn	synonymous_variant	Exon 13 of 24	ENST00000551295.7	NP_001834.2	Q12860-1A0A024R104

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN1	ENST00000551295.7 link	c.1416C>T	p.Asn472Asn	synonymous_variant	Exon 13 of 24	1	NM_001843.4	ENSP00000447006.1		Q12860-1

Frequencies

GnomAD3 genomes

AF:

0.621

AC:

94288

AN:

151734

Hom.:

29414

Cov.:

show subpopulations

Gnomad AFR

AF:

0.591

Gnomad AMI

AF:

0.640

Gnomad AMR

AF:

0.660

Gnomad ASJ

AF:

0.664

Gnomad EAS

AF:

0.470

Gnomad SAS

AF:

0.550

Gnomad FIN

AF:

0.682

Gnomad MID

AF:

0.690

Gnomad NFE

AF:

0.636

Gnomad OTH

AF:

0.619

GnomAD2 exomes

AF:

0.621

AC:

155177

AN:

249942

AF XY:

0.618

show subpopulations

Gnomad AFR exome

AF:

0.584

Gnomad AMR exome

AF:

0.691

Gnomad ASJ exome

AF:

0.666

Gnomad EAS exome

AF:

0.462

Gnomad FIN exome

AF:

0.683

Gnomad NFE exome

AF:

0.636

Gnomad OTH exome

AF:

0.638

GnomAD4 exome

AF:

0.618

AC:

889684

AN:

1440126

Hom.:

276512

Cov.:

AF XY:

0.617

AC XY:

442770

AN XY:

717712

show subpopulations

African (AFR)

AF:

0.587

AC:

19388

AN:

33010

American (AMR)

AF:

0.682

AC:

30436

AN:

44610

Ashkenazi Jewish (ASJ)

AF:

0.670

AC:

17376

AN:

25934

East Asian (EAS)

AF:

0.457

AC:

18041

AN:

39484

South Asian (SAS)

AF:

0.542

AC:

46535

AN:

85784

European-Finnish (FIN)

AF:

0.682

AC:

36371

AN:

53352

Middle Eastern (MID)

AF:

0.696

AC:

3975

AN:

5710

European-Non Finnish (NFE)

AF:

0.623

AC:

680753

AN:

1092580

Other (OTH)

AF:

0.617

AC:

36809

AN:

59662

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

15882

31765

47647

63530

79412

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.621

AC:

94323

AN:

151850

Hom.:

29423

Cov.:

AF XY:

0.622

AC XY:

46118

AN XY:

74174

show subpopulations

African (AFR)

AF:

0.591

AC:

24484

AN:

41438

American (AMR)

AF:

0.661

AC:

10041

AN:

15202

Ashkenazi Jewish (ASJ)

AF:

0.664

AC:

2305

AN:

3472

East Asian (EAS)

AF:

0.470

AC:

2432

AN:

5174

South Asian (SAS)

AF:

0.550

AC:

2648

AN:

4818

European-Finnish (FIN)

AF:

0.682

AC:

7177

AN:

10528

Middle Eastern (MID)

AF:

0.690

AC:

203

AN:

294

European-Non Finnish (NFE)

AF:

0.636

AC:

43169

AN:

67916

Other (OTH)

AF:

0.611

AC:

1283

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1872

3744

5617

7489

9361

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.630

Hom.:

58375

Bravo

AF:

0.618

Asia WGS

AF:

0.497

AC:

1727

AN:

3472

EpiCase

AF:

0.640

EpiControl

AF:

0.641

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 05, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Compton-North congenital myopathy

Benign:2

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

4.9

(source)

DANN

Benign

0.37

PhyloP100

-0.56

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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12-40943633-C-T

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