rs2229930

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.1956A>G(p.Ala652Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0414 in 1,612,264 control chromosomes in the GnomAD database, including 1,611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 110 hom., cov: 32)

Exomes 𝑓: 0.042 ( 1501 hom. )

Consequence

CNTN1
NM_001843.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.71

Publications

6 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=-0.74).

BP6

Variant 12-40981060-A-G is Benign according to our data. Variant chr12-40981060-A-G is described in ClinVar as Benign. ClinVar VariationId is 128793.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.71 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN1	NM_001843.4 link	c.1956A>G	p.Ala652Ala	synonymous_variant	Exon 16 of 24	ENST00000551295.7	NP_001834.2	Q12860-1A0A024R104

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CNTN1	ENST00000551295.7 link	c.1956A>G	p.Ala652Ala	synonymous_variant	Exon 16 of 24	1	NM_001843.4	ENSP00000447006.1	Q12860-1
CNTN1	ENST00000347616.5 link	c.1956A>G	p.Ala652Ala	synonymous_variant	Exon 15 of 23	1		ENSP00000325660.3	Q12860-1
CNTN1	ENST00000348761.2 link	c.1923A>G	p.Ala641Ala	synonymous_variant	Exon 14 of 22	1		ENSP00000261160.3	Q12860-2

Frequencies

GnomAD3 genomes

AF:

0.0332

AC:

5055

AN:

152244

Hom.:

110

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00846

Gnomad AMI

AF:

0.0855

Gnomad AMR

AF:

0.0468

Gnomad ASJ

AF:

0.0458

Gnomad EAS

AF:

0.00653

Gnomad SAS

AF:

0.0554

Gnomad FIN

AF:

0.0203

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0458

Gnomad OTH

AF:

0.0402

GnomAD2 exomes

AF:

0.0399

AC:

10004

AN:

250718

AF XY:

0.0415

show subpopulations

Gnomad AFR exome

AF:

0.00806

Gnomad AMR exome

AF:

0.0463

Gnomad ASJ exome

AF:

0.0515

Gnomad EAS exome

AF:

0.00500

Gnomad FIN exome

AF:

0.0214

Gnomad NFE exome

AF:

0.0458

Gnomad OTH exome

AF:

0.0507

GnomAD4 exome

AF:

0.0422

AC:

61649

AN:

1459902

Hom.:

1501

Cov.:

AF XY:

0.0429

AC XY:

31146

AN XY:

726274

show subpopulations

African (AFR)

AF:

0.00814

AC:

272

AN:

33430

American (AMR)

AF:

0.0485

AC:

2167

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.0501

AC:

1308

AN:

26114

East Asian (EAS)

AF:

0.00542

AC:

215

AN:

39672

South Asian (SAS)

AF:

0.0561

AC:

4837

AN:

86196

European-Finnish (FIN)

AF:

0.0208

AC:

1110

AN:

53402

Middle Eastern (MID)

AF:

0.0922

AC:

444

AN:

4814

European-Non Finnish (NFE)

AF:

0.0440

AC:

48890

AN:

1111336

Other (OTH)

AF:

0.0399

AC:

2406

AN:

60248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

2741

5481

8222

10962

13703

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1808

3616

5424

7232

9040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0332

AC:

5059

AN:

152362

Hom.:

110

Cov.:

AF XY:

0.0331

AC XY:

2469

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.00849

AC:

353

AN:

41592

American (AMR)

AF:

0.0467

AC:

715

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0458

AC:

159

AN:

3472

East Asian (EAS)

AF:

0.00655

AC:

AN:

5194

South Asian (SAS)

AF:

0.0563

AC:

272

AN:

4834

European-Finnish (FIN)

AF:

0.0203

AC:

216

AN:

10626

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0458

AC:

3116

AN:

68026

Other (OTH)

AF:

0.0393

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

251

502

752

1003

1254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0418

Hom.:

132

Bravo

AF:

0.0340

Asia WGS

AF:

0.0290

AC:

102

AN:

3476

EpiCase

AF:

0.0457

EpiControl

AF:

0.0484

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 17, 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. -

Aug 20, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Compton-North congenital myopathy

Benign:1

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

-0.74

CADD

Benign

0.45

(source)

DANN

Benign

0.56

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism (auto)

(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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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