Genetic Variant CNTN1:c.62-50A>C (chr12-40910023-A-C) – 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.62-50A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,376,668 control chromosomes in the GnomAD database, including 58,353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4978 hom., cov: 32)

Exomes 𝑓: 0.29 ( 53375 hom. )

Consequence

CNTN1
NM_001843.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.645

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:

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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 12-40910023-A-C is Benign according to our data. Variant chr12-40910023-A-C is described in ClinVar as [Benign]. Clinvar id is 680155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN1	NM_001843.4 link	c.62-50A>C		intron_variant	Intron 2 of 23	ENST00000551295.7	NP_001834.2	Q12860-1A0A024R104

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN1	ENST00000551295.7 link	c.62-50A>C		intron_variant	Intron 2 of 23	1	NM_001843.4	ENSP00000447006.1		Q12860-1

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

36353

AN:

151904

Hom.:

4988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0993

Gnomad AMI

AF:

0.265

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.363

Gnomad EAS

AF:

0.227

Gnomad SAS

AF:

0.331

Gnomad FIN

AF:

0.261

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.270

GnomAD3 exomes

AF:

0.270

AC:

67223

AN:

248762

Hom.:

9943

AF XY:

0.281

AC XY:

37891

AN XY:

134670

show subpopulations

Gnomad AFR exome

AF:

0.0921

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.365

Gnomad EAS exome

AF:

0.224

Gnomad SAS exome

AF:

0.320

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.316

Gnomad OTH exome

AF:

0.300

GnomAD4 exome

AF:

0.291

AC:

356110

AN:

1224646

Hom.:

53375

Cov.:

AF XY:

0.295

AC XY:

183068

AN XY:

621364

show subpopulations

Gnomad4 AFR exome

AF:

0.0935

Gnomad4 AMR exome

AF:

0.165

Gnomad4 ASJ exome

AF:

0.370

Gnomad4 EAS exome

AF:

0.203

Gnomad4 SAS exome

AF:

0.320

Gnomad4 FIN exome

AF:

0.270

Gnomad4 NFE exome

AF:

0.303

Gnomad4 OTH exome

AF:

0.293

GnomAD4 genome

AF:

0.239

AC:

36334

AN:

152022

Hom.:

4978

Cov.:

AF XY:

0.238

AC XY:

17720

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.0991

Gnomad4 AMR

AF:

0.224

Gnomad4 ASJ

AF:

0.363

Gnomad4 EAS

AF:

0.227

Gnomad4 SAS

AF:

0.330

Gnomad4 FIN

AF:

0.261

Gnomad4 NFE

AF:

0.311

Gnomad4 OTH

AF:

0.267

Alfa

AF:

0.289

Hom.:

2047

Bravo

AF:

0.225

Asia WGS

AF:

0.248

AC:

860

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 14, 2018

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.1

DANN

Benign

0.69

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