Variant 3-3040275-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_175607.3(CNTN4):c.2398+4T>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0985 in 1,579,766 control chromosomes in the GnomAD database, including 9,346 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2082 hom., cov: 34)

Exomes 𝑓: 0.094 ( 7264 hom. )

Consequence

CNTN4
NM_175607.3 splice_donor_region, intron

Scores

Splicing: ADA: 0.00003434

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.483

Variant links:

Genes affected

CNTN4 (HGNC:2174): (contactin 4) This gene encodes a member of the contactin family of immunoglobulins. Contactins are axon-associated cell adhesion molecules that function in neuronal network formation and plasticity. The encoded protein is a glycosylphosphatidylinositol-anchored neuronal membrane protein that may play a role in the formation of axon connections in the developing nervous system. Deletion or mutation of this gene may play a role in 3p deletion syndrome and autism spectrum disorders. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2011]

CNTN4 links:

CNTN4-AS1 (HGNC:39985): (CNTN4 antisense RNA 1)

CNTN4-AS1 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=-0.88).

BP6

Variant 3-3040275-T-C is Benign according to our data. Variant chr3-3040275-T-C is described in ClinVar as [Benign]. Clinvar id is 1221661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN4	NM_175607.3 linkuse as main transcript	c.2398+4T>C		splice_donor_region_variant, intron_variant		ENST00000418658.6	NP_783200.1
CNTN4-AS1	NR_046554.1 linkuse as main transcript	n.398A>G		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6 linkuse as main transcript	c.2398+4T>C		splice_donor_region_variant, intron_variant		5	NM_175607.3	ENSP00000396010	P1	Q8IWV2-1

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21143

AN:

152198

Hom.:

2076

Cov.:

show subpopulations

Gnomad AFR

AF:

0.276

Gnomad AMI

AF:

0.0637

Gnomad AMR

AF:

0.111

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0600

Gnomad FIN

AF:

0.0486

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.0936

Gnomad OTH

AF:

0.130

GnomAD3 exomes

AF:

0.0893

AC:

22416

AN:

251102

Hom.:

1498

AF XY:

0.0865

AC XY:

11736

AN XY:

135708

show subpopulations

Gnomad AFR exome

AF:

0.283

Gnomad AMR exome

AF:

0.0622

Gnomad ASJ exome

AF:

0.146

Gnomad EAS exome

AF:

0.00147

Gnomad SAS exome

AF:

0.0686

Gnomad FIN exome

AF:

0.0523

Gnomad NFE exome

AF:

0.0911

Gnomad OTH exome

AF:

0.0976

GnomAD4 exome

AF:

0.0942

AC:

134410

AN:

1427450

Hom.:

7264

Cov.:

AF XY:

0.0929

AC XY:

66186

AN XY:

712454

show subpopulations

Gnomad4 AFR exome

AF:

0.284

Gnomad4 AMR exome

AF:

0.0662

Gnomad4 ASJ exome

AF:

0.151

Gnomad4 EAS exome

AF:

0.000607

Gnomad4 SAS exome

AF:

0.0679

Gnomad4 FIN exome

AF:

0.0511

Gnomad4 NFE exome

AF:

0.0952

Gnomad4 OTH exome

AF:

0.102

GnomAD4 genome

AF:

0.139

AC:

21172

AN:

152316

Hom.:

2082

Cov.:

AF XY:

0.134

AC XY:

10014

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.276

Gnomad4 AMR

AF:

0.110

Gnomad4 ASJ

AF:

0.132

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0604

Gnomad4 FIN

AF:

0.0486

Gnomad4 NFE

AF:

0.0936

Gnomad4 OTH

AF:

0.128

Alfa

AF:

0.109

Hom.:

1463

Bravo

AF:

0.148

Asia WGS

AF:

0.0420

AC:

147

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

CNTN4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 29, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.54

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000034

dbscSNV1_RF

Benign

0.0080

SpliceAI score (max)

0.010

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