dbSNP rs12367345: CNTN1:c.2711-17A>G (chr12-41027840-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001843.4(CNTN1):c.2711-17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,492,160 control chromosomes in the GnomAD database, including 16,623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1290 hom., cov: 32)

Exomes 𝑓: 0.15 ( 15333 hom. )

Consequence

CNTN1
NM_001843.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.547

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 12-41027840-A-G is Benign according to our data. Variant chr12-41027840-A-G is described in ClinVar as [Benign]. Clinvar id is 258196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN1	NM_001843.4 link	c.2711-17A>G		intron_variant	Intron 21 of 23	ENST00000551295.7	NP_001834.2	Q12860-1A0A024R104

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CNTN1	ENST00000551295.7 link	c.2711-17A>G	intron_variant	Intron 21 of 23	1	NM_001843.4	ENSP00000447006.1	Q12860-1
CNTN1	ENST00000347616.5 link	c.2711-17A>G	intron_variant	Intron 20 of 22	1		ENSP00000325660.3	Q12860-1
CNTN1	ENST00000348761.2 link	c.2678-17A>G	intron_variant	Intron 19 of 21	1		ENSP00000261160.3	Q12860-2
CNTN1	ENST00000550305.1 link	n.670-17A>G	intron_variant	Intron 5 of 5	3

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18308

AN:

152016

Hom.:

1289

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0543

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.116

Gnomad EAS

AF:

0.0720

Gnomad SAS

AF:

0.0789

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.124

GnomAD3 exomes

AF:

0.128

AC:

32092

AN:

250542

Hom.:

2301

AF XY:

0.129

AC XY:

17464

AN XY:

135402

show subpopulations

Gnomad AFR exome

AF:

0.0521

Gnomad AMR exome

AF:

0.110

Gnomad ASJ exome

AF:

0.112

Gnomad EAS exome

AF:

0.0750

Gnomad SAS exome

AF:

0.0775

Gnomad FIN exome

AF:

0.190

Gnomad NFE exome

AF:

0.156

Gnomad OTH exome

AF:

0.132

GnomAD4 exome

AF:

0.147

AC:

196985

AN:

1340026

Hom.:

15333

Cov.:

AF XY:

0.145

AC XY:

97783

AN XY:

673624

show subpopulations

Gnomad4 AFR exome

AF:

0.0518

Gnomad4 AMR exome

AF:

0.110

Gnomad4 ASJ exome

AF:

0.111

Gnomad4 EAS exome

AF:

0.0571

Gnomad4 SAS exome

AF:

0.0811

Gnomad4 FIN exome

AF:

0.186

Gnomad4 NFE exome

AF:

0.160

Gnomad4 OTH exome

AF:

0.136

GnomAD4 genome

AF:

0.120

AC:

18308

AN:

152134

Hom.:

1290

Cov.:

AF XY:

0.120

AC XY:

8957

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0542

Gnomad4 AMR

AF:

0.117

Gnomad4 ASJ

AF:

0.116

Gnomad4 EAS

AF:

0.0717

Gnomad4 SAS

AF:

0.0790

Gnomad4 FIN

AF:

0.195

Gnomad4 NFE

AF:

0.157

Gnomad4 OTH

AF:

0.123

Alfa

AF:

0.140

Hom.:

961

Bravo

AF:

0.113

Asia WGS

AF:

0.0750

AC:

260

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 08, 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. -

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

-0.86

CADD

Benign

0.021

DANN

Benign

0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over