dbSNP rs148387796: CNTN1:c.401-14delT (chr12-40924536-CT-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001843.4(CNTN1):c.401-14delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00399 in 1,325,184 control chromosomes in the GnomAD database, including 14 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 3 hom., cov: 29)

Exomes 𝑓: 0.0041 ( 11 hom. )

Consequence

CNTN1
NM_001843.4 intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: -0.197

Publications

0 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 -16 ACMG points.

BP6

Variant 12-40924536-CT-C is Benign according to our data. Variant chr12-40924536-CT-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00284 (432/151910) while in subpopulation NFE AF = 0.0053 (360/67920). AF 95% confidence interval is 0.00485. There are 3 homozygotes in GnomAd4. There are 183 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN1	NM_001843.4 link	c.401-14delT		intron_variant	Intron 5 of 23	ENST00000551295.7	NP_001834.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN1	ENST00000551295.7 link	c.401-20delT		intron_variant	Intron 5 of 23	1	NM_001843.4	ENSP00000447006.1

Frequencies

GnomAD3 genomes

AF:

0.00285

AC:

432

AN:

151792

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000750

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000756

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00530

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00252

AC:

595

AN:

236036

AF XY:

0.00240

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.00180

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00138

Gnomad NFE exome

AF:

0.00437

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00414

AC:

4861

AN:

1173274

Hom.:

Cov.:

AF XY:

0.00397

AC XY:

2375

AN XY:

597576

show subpopulations

African (AFR)

AF:

0.000831

AC:

AN:

27664

American (AMR)

AF:

0.00216

AC:

AN:

43458

Ashkenazi Jewish (ASJ)

AF:

0.0000415

AC:

AN:

24112

East Asian (EAS)

AF:

0.00

AC:

AN:

37912

South Asian (SAS)

AF:

0.000468

AC:

AN:

79042

European-Finnish (FIN)

AF:

0.00173

AC:

AN:

52670

Middle Eastern (MID)

AF:

0.000192

AC:

AN:

5198

European-Non Finnish (NFE)

AF:

0.00522

AC:

4447

AN:

852658

Other (OTH)

AF:

0.00330

AC:

167

AN:

50560

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

240

479

719

958

1198

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

276

414

552

690

<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:

0.00284

AC:

432

AN:

151910

Hom.:

Cov.:

AF XY:

0.00247

AC XY:

183

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.000748

AC:

AN:

41432

American (AMR)

AF:

0.00177

AC:

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.000756

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00530

AC:

360

AN:

67920

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00164

Hom.:

Bravo

AF:

0.00289

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Compton-North congenital myopathy

Benign:1

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Apr 26, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.20

Mutation Taster

=100/0

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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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