Variant 12-41029168-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001843.4(CNTN1):c.2929C>T(p.Arg977Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000423 in 1,613,902 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 3 hom. )

Consequence

CNTN1
NM_001843.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.14

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01847151).

BP6

Variant 12-41029168-C-T is Benign according to our data. Variant chr12-41029168-C-T is described in ClinVar as [Benign]. Clinvar id is 469422.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000441 (67/152052) while in subpopulation AMR AF= 0.000328 (5/15238). AF 95% confidence interval is 0.000129. There are 0 homozygotes in gnomad4. There are 30 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN1	NM_001843.4 linkuse as main transcript	c.2929C>T	p.Arg977Cys	missense_variant	23/24	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.2929C>T	p.Arg977Cys	missense_variant	23/24	1	NM_001843.4	ENSP00000447006.1	Q12860-1
CNTN1	ENST00000347616.5 linkuse as main transcript	c.2929C>T	p.Arg977Cys	missense_variant	22/23	1		ENSP00000325660.3	Q12860-1
CNTN1	ENST00000348761.2 linkuse as main transcript	c.2896C>T	p.Arg966Cys	missense_variant	21/22	1		ENSP00000261160.3	Q12860-2
CNTN1	ENST00000548481.1 linkuse as main transcript	n.55C>T		non_coding_transcript_exon_variant	1/3	3		ENSP00000449517.1	H0YIJ1

Frequencies

GnomAD3 genomes

AF:

0.000441

AC:

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000788

AC:

198

AN:

251176

Hom.:

AF XY:

0.000715

AC XY:

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.0161

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000247

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000421

AC:

615

AN:

1461850

Hom.:

Cov.:

AF XY:

0.000413

AC XY:

300

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.0147

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000131

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.000441

AC:

AN:

152052

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.000328

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000785

Hom.:

Bravo

AF:

0.000472

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000519

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Compton-North congenital myopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 25, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Uncertain

0.069

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.86

D;D;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.98

.;D;D

M_CAP

Uncertain

0.087

MetaRNN

Benign

0.018

T;T;T

MetaSVM

Benign

-0.47

MutationAssessor

Uncertain

2.1

M;M;.

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-6.5

D;D;D

REVEL

Uncertain

0.42

Sift

Uncertain

0.018

D;D;D

Sift4G

Uncertain

0.056

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.78

MVP

0.72

MPC

1.2

ClinPred

0.15

GERP RS

5.2

Varity_R

0.44

gMVP

0.81

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