Variant rs61759480 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001843.4(CNTN1):c.1401T>C(p.Gly467=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00341 in 1,588,330 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 23 hom. )

Consequence

CNTN1
NM_001843.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.82

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 12-40943618-T-C is Benign according to our data. Variant chr12-40943618-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 258192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.82 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00204 (310/152196) while in subpopulation NFE AF= 0.00349 (237/67998). AF 95% confidence interval is 0.00312. There are 1 homozygotes in gnomad4. There are 126 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN1	NM_001843.4 linkuse as main transcript	c.1401T>C	p.Gly467=	synonymous_variant	13/24	ENST00000551295.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN1	ENST00000551295.7 linkuse as main transcript	c.1401T>C	p.Gly467=	synonymous_variant	13/24	1	NM_001843.4	P3	Q12860-1

Frequencies

GnomAD3 genomes

AF:

0.00204

AC:

310

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000395

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00273

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00348

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00190

AC:

475

AN:

249892

Hom.:

AF XY:

0.00194

AC XY:

262

AN XY:

135038

show subpopulations

Gnomad AFR exome

AF:

0.000987

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00245

Gnomad NFE exome

AF:

0.00341

Gnomad OTH exome

AF:

0.00197

GnomAD4 exome

AF:

0.00356

AC:

5111

AN:

1436134

Hom.:

Cov.:

AF XY:

0.00346

AC XY:

2479

AN XY:

716070

show subpopulations

Gnomad4 AFR exome

AF:

0.000486

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.000116

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00300

Gnomad4 NFE exome

AF:

0.00441

Gnomad4 OTH exome

AF:

0.00212

GnomAD4 genome

AF:

0.00204

AC:

310

AN:

152196

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

126

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.000394

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00273

Gnomad4 NFE

AF:

0.00349

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00296

Hom.:

Bravo

AF:

0.00198

EpiCase

AF:

0.00219

EpiControl

AF:

0.00267

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 22, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	CNTN1: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 06, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Compton-North congenital myopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.2

DANN

Benign

0.63

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