12-41016821-G-A

Position:

chr12-41016821-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001843.4(CNTN1):c.2324G>A(p.Ser775Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00171 in 1,614,034 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0091 ( 23 hom., cov: 32)

Exomes 𝑓: 0.00094 ( 25 hom. )

Consequence

CNTN1
NM_001843.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.15

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:

CNTN1 (HGNC:):

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 (MetaRNN=0.0043031573).

BP6

Variant 12-41016821-G-A is Benign according to our data. Variant chr12-41016821-G-A is described in ClinVar as [Benign]. Clinvar id is 128794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00911 (1387/152186) while in subpopulation AFR AF= 0.0311 (1289/41508). AF 95% confidence interval is 0.0296. There are 23 homozygotes in gnomad4. There are 628 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN1	NM_001843.4 linkuse as main transcript	c.2324G>A	p.Ser775Asn	missense_variant	19/24	ENST00000551295.7	NP_001834.2	Q12860-1A0A024R104

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CNTN1	ENST00000551295.7 linkuse as main transcript	c.2324G>A	p.Ser775Asn	missense_variant	19/24	1	NM_001843.4	ENSP00000447006.1	Q12860-1
CNTN1	ENST00000347616.5 linkuse as main transcript	c.2324G>A	p.Ser775Asn	missense_variant	18/23	1		ENSP00000325660.3	Q12860-1
CNTN1	ENST00000348761.2 linkuse as main transcript	c.2291G>A	p.Ser764Asn	missense_variant	17/22	1		ENSP00000261160.3	Q12860-2
CNTN1	ENST00000550305.1 linkuse as main transcript	n.283G>A		non_coding_transcript_exon_variant	3/6	3

Frequencies

GnomAD3 genomes

AF:

0.00909

AC:

1383

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0310

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00452

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00861

GnomAD3 exomes

AF:

0.00247

AC:

620

AN:

251398

Hom.:

AF XY:

0.00178

AC XY:

242

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.0336

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.000979

GnomAD4 exome

AF:

0.000938

AC:

1371

AN:

1461848

Hom.:

Cov.:

AF XY:

0.000815

AC XY:

593

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0331

Gnomad4 AMR exome

AF:

0.00201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000324

Gnomad4 OTH exome

AF:

0.00190

GnomAD4 genome

AF:

0.00911

AC:

1387

AN:

152186

Hom.:

Cov.:

AF XY:

0.00844

AC XY:

628

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0311

Gnomad4 AMR

AF:

0.00451

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00852

Alfa

AF:

0.00232

Hom.:

Bravo

AF:

0.0102

ESP6500AA

AF:

0.0338

AC:

149

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00311

AC:

378

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Oct 29, 2019	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 23, 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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Compton-North congenital myopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.30

T;T;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.78

.;T;T

MetaRNN

Benign

0.0043

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;N;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.93

N;N;N

REVEL

Benign

0.087

Sift

Benign

0.38

T;T;T

Sift4G

Benign

0.32

T;T;T

Polyphen

0.076

B;B;B

Vest4

0.14

MVP

0.35

MPC

0.32

ClinPred

0.0084

GERP RS

2.2

Varity_R

0.082

gMVP

0.33

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