Variant 3-3040141-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_175607.3(CNTN4):c.2268T>C(p.Asp756=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 1,613,992 control chromosomes in the GnomAD database, including 666,908 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.92 ( 64765 hom., cov: 33)

Exomes 𝑓: 0.91 ( 602143 hom. )

Consequence

CNTN4
NM_175607.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.94

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 3-3040141-T-C is Benign according to our data. Variant chr3-3040141-T-C is described in ClinVar as [Benign]. Clinvar id is 1288044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.94 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.953 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.2268T>C	p.Asp756=	synonymous_variant	20/25	ENST00000418658.6	NP_783200.1
CNTN4-AS1	NR_046554.1 linkuse as main transcript	n.532A>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.2268T>C	p.Asp756=	synonymous_variant	20/25	5	NM_175607.3	ENSP00000396010	P1	Q8IWV2-1

Frequencies

GnomAD3 genomes

AF:

0.921

AC:

140236

AN:

152194

Hom.:

64715

Cov.:

show subpopulations

Gnomad AFR

AF:

0.961

Gnomad AMI

AF:

0.940

Gnomad AMR

AF:

0.907

Gnomad ASJ

AF:

0.909

Gnomad EAS

AF:

0.883

Gnomad SAS

AF:

0.809

Gnomad FIN

AF:

0.883

Gnomad MID

AF:

0.927

Gnomad NFE

AF:

0.917

Gnomad OTH

AF:

0.932

GnomAD3 exomes

AF:

0.894

AC:

224930

AN:

251484

Hom.:

100934

AF XY:

0.891

AC XY:

121046

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.963

Gnomad AMR exome

AF:

0.876

Gnomad ASJ exome

AF:

0.905

Gnomad EAS exome

AF:

0.885

Gnomad SAS exome

AF:

0.808

Gnomad FIN exome

AF:

0.875

Gnomad NFE exome

AF:

0.918

Gnomad OTH exome

AF:

0.899

GnomAD4 exome

AF:

0.907

AC:

1325654

AN:

1461682

Hom.:

602143

Cov.:

AF XY:

0.904

AC XY:

657264

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.966

Gnomad4 AMR exome

AF:

0.880

Gnomad4 ASJ exome

AF:

0.908

Gnomad4 EAS exome

AF:

0.893

Gnomad4 SAS exome

AF:

0.809

Gnomad4 FIN exome

AF:

0.878

Gnomad4 NFE exome

AF:

0.916

Gnomad4 OTH exome

AF:

0.902

GnomAD4 genome

AF:

0.921

AC:

140344

AN:

152310

Hom.:

64765

Cov.:

AF XY:

0.917

AC XY:

68259

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.961

Gnomad4 AMR

AF:

0.907

Gnomad4 ASJ

AF:

0.909

Gnomad4 EAS

AF:

0.883

Gnomad4 SAS

AF:

0.808

Gnomad4 FIN

AF:

0.883

Gnomad4 NFE

AF:

0.917

Gnomad4 OTH

AF:

0.931

Alfa

AF:

0.916

Hom.:

114389

Bravo

AF:

0.927

Asia WGS

AF:

0.818

AC:

2847

AN:

3478

EpiCase

AF:

0.913

EpiControl

AF:

0.915

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 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.12

DANN

Benign

0.62

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