rs1056019

chr12-40943633-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001843.4(CNTN1):c.1416C>T(p.Asn472=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.557

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]

ACMG classification

Verdict is Benign. Variant got -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. Variant chr12-40943633-C-T is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
CNTN1	NM_001843.4	c.1416C>T	p.Asn472=	synonymous_variant	13/24	ENST00000551295.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN1	ENST00000551295.7	c.1416C>T	p.Asn472=	synonymous_variant	13/24	1	NM_001843.4	P3

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94288 AN: 151734 Hom.: 29414 Cov.: 32

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

GnomAD3 exomes AF: 0.621 AC: 155177 AN: 249942 Hom.: 48729 AF XY: 0.618 AC XY: 83439 AN XY: 135070

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 SAS exome AF: 0.537

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.: 32 AF XY: 0.617 AC XY: 442770 AN XY: 717712

Gnomad4 AFR exome AF: 0.587

Gnomad4 AMR exome AF: 0.682

Gnomad4 ASJ exome AF: 0.670

Gnomad4 EAS exome AF: 0.457

Gnomad4 SAS exome AF: 0.542

Gnomad4 FIN exome AF: 0.682

Gnomad4 NFE exome AF: 0.623

Gnomad4 OTH exome AF: 0.617

GnomAD4 genome AF: 0.621 AC: 94323 AN: 151850 Hom.: 29423 Cov.: 32 AF XY: 0.622 AC XY: 46118 AN XY: 74174

Gnomad4 AFR AF: 0.591

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.664

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.682

Gnomad4 NFE AF: 0.636

Gnomad4 OTH AF: 0.611

Alfa AF: 0.631 Hom.: 50839

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:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 05, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -

Compton-North congenital myopathy Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	4.9
Dann	Benign	0.37

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

LitVar

Other links and lift over

dbSNP: rs1056019; hg19: chr12-41337435; COSMIC: COSV61637004;