Variant 3-3040452-G-A 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+181G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 644,360 control chromosomes in the GnomAD database, including 4,651 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2171 hom., cov: 33)

Exomes 𝑓: 0.088 ( 2480 hom. )

Consequence

CNTN4
NM_175607.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.78

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:

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 (BayesDel_noAF=-0.97).

BP6

Variant 3-3040452-G-A is Benign according to our data. Variant chr3-3040452-G-A is described in ClinVar as [Benign]. Clinvar id is 1276669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 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+181G>A		intron_variant		ENST00000418658.6	NP_783200.1
CNTN4-AS1	NR_046554.1 linkuse as main transcript	n.291-70C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6 linkuse as main transcript	c.2398+181G>A		intron_variant		5	NM_175607.3	ENSP00000396010	P1	Q8IWV2-1

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21480

AN:

152056

Hom.:

2162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.284

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0603

Gnomad FIN

AF:

0.0486

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.0936

Gnomad OTH

AF:

0.131

GnomAD4 exome

AF:

0.0884

AC:

43521

AN:

492186

Hom.:

2480

AF XY:

0.0871

AC XY:

22791

AN XY:

261696

show subpopulations

Gnomad4 AFR exome

AF:

0.285

Gnomad4 AMR exome

AF:

0.0696

Gnomad4 ASJ exome

AF:

0.147

Gnomad4 EAS exome

AF:

0.000555

Gnomad4 SAS exome

AF:

0.0670

Gnomad4 FIN exome

AF:

0.0497

Gnomad4 NFE exome

AF:

0.0930

Gnomad4 OTH exome

AF:

0.104

GnomAD4 genome

AF:

0.141

AC:

21521

AN:

152174

Hom.:

2171

Cov.:

AF XY:

0.137

AC XY:

10194

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.285

Gnomad4 AMR

AF:

0.111

Gnomad4 ASJ

AF:

0.132

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0605

Gnomad4 FIN

AF:

0.0486

Gnomad4 NFE

AF:

0.0936

Gnomad4 OTH

AF:

0.129

Alfa

AF:

0.123

Hom.:

177

Bravo

AF:

0.151

Asia WGS

AF:

0.0430

AC:

150

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.94

DANN

Benign

0.79

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