chr12-40936809-T-C

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.1014T>C(p.Asn338Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,612,934 control chromosomes in the GnomAD database, including 12,701 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1453 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11248 hom. )

Consequence

CNTN1
NM_001843.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.171

Publications

14 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=-0.5).

BP6

Variant 12-40936809-T-C is Benign according to our data. Variant chr12-40936809-T-C is described in ClinVar as Benign. ClinVar VariationId is 128790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.171 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN1	NM_001843.4 link	c.1014T>C	p.Asn338Asn	synonymous_variant	Exon 10 of 24	ENST00000551295.7	NP_001834.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN1	ENST00000551295.7 link	c.1014T>C	p.Asn338Asn	synonymous_variant	Exon 10 of 24	1	NM_001843.4	ENSP00000447006.1

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20497

AN:

152042

Hom.:

1454

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.0989

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.146

Gnomad EAS

AF:

0.0628

Gnomad SAS

AF:

0.0731

Gnomad FIN

AF:

0.154

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.129

GnomAD2 exomes

AF:

0.116

AC:

29040

AN:

250680

AF XY:

0.114

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.107

Gnomad ASJ exome

AF:

0.140

Gnomad EAS exome

AF:

0.0655

Gnomad FIN exome

AF:

0.153

Gnomad NFE exome

AF:

0.121

Gnomad OTH exome

AF:

0.120

GnomAD4 exome

AF:

0.121

AC:

177446

AN:

1460774

Hom.:

11248

Cov.:

AF XY:

0.120

AC XY:

87103

AN XY:

726676

show subpopulations

African (AFR)

AF:

0.171

AC:

5706

AN:

33432

American (AMR)

AF:

0.107

AC:

4766

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.138

AC:

3592

AN:

26096

East Asian (EAS)

AF:

0.0515

AC:

2042

AN:

39682

South Asian (SAS)

AF:

0.0763

AC:

6585

AN:

86248

European-Finnish (FIN)

AF:

0.149

AC:

7936

AN:

53396

Middle Eastern (MID)

AF:

0.113

AC:

650

AN:

5758

European-Non Finnish (NFE)

AF:

0.125

AC:

138791

AN:

1111180

Other (OTH)

AF:

0.122

AC:

7378

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

8124

16248

24373

32497

40621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5166

10332

15498

20664

25830

<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:

0.135

AC:

20512

AN:

152160

Hom.:

1453

Cov.:

AF XY:

0.134

AC XY:

9994

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.171

AC:

7097

AN:

41504

American (AMR)

AF:

0.122

AC:

1862

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.146

AC:

508

AN:

3468

East Asian (EAS)

AF:

0.0624

AC:

323

AN:

5180

South Asian (SAS)

AF:

0.0734

AC:

354

AN:

4826

European-Finnish (FIN)

AF:

0.154

AC:

1633

AN:

10592

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.123

AC:

8349

AN:

68008

Other (OTH)

AF:

0.127

AC:

269

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

905

1810

2716

3621

4526

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<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:

0.127

Hom.:

969

Bravo

AF:

0.136

Asia WGS

AF:

0.0810

AC:

281

AN:

3478

EpiCase

AF:

0.120

EpiControl

AF:

0.122

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

- -

Jan 26, 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 15, 2013

Genetic Services Laboratory, University of Chicago

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

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

5.9

(source)

DANN

Benign

0.65

PhyloP100

0.17

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