Variant 3-3040066-A-T 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.2193A>T(p.Arg731=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,611,044 control chromosomes in the GnomAD database, including 138,038 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9959 hom., cov: 34)

Exomes 𝑓: 0.41 ( 128079 hom. )

Consequence

CNTN4
NM_175607.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.441

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=-0.52).

BP6

Variant 3-3040066-A-T is Benign according to our data. Variant chr3-3040066-A-T is described in ClinVar as [Benign]. Clinvar id is 1286695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.441 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.561 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.2193A>T	p.Arg731=	synonymous_variant	20/25	ENST00000418658.6	NP_783200.1
CNTN4-AS1	NR_046554.1 linkuse as main transcript	n.607T>A		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.2193A>T	p.Arg731=	synonymous_variant	20/25	5	NM_175607.3	ENSP00000396010	P1	Q8IWV2-1

Frequencies

GnomAD3 genomes

AF:

0.337

AC:

51220

AN:

152026

Hom.:

9961

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.395

Gnomad AMR

AF:

0.383

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.578

Gnomad SAS

AF:

0.467

Gnomad FIN

AF:

0.390

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.413

Gnomad OTH

AF:

0.353

GnomAD3 exomes

AF:

0.408

AC:

102506

AN:

251420

Hom.:

22125

AF XY:

0.414

AC XY:

56270

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.439

Gnomad ASJ exome

AF:

0.275

Gnomad EAS exome

AF:

0.564

Gnomad SAS exome

AF:

0.462

Gnomad FIN exome

AF:

0.388

Gnomad NFE exome

AF:

0.416

Gnomad OTH exome

AF:

0.376

GnomAD4 exome

AF:

0.413

AC:

602697

AN:

1458900

Hom.:

128079

Cov.:

AF XY:

0.415

AC XY:

301062

AN XY:

725976

show subpopulations

Gnomad4 AFR exome

AF:

0.119

Gnomad4 AMR exome

AF:

0.435

Gnomad4 ASJ exome

AF:

0.279

Gnomad4 EAS exome

AF:

0.587

Gnomad4 SAS exome

AF:

0.457

Gnomad4 FIN exome

AF:

0.389

Gnomad4 NFE exome

AF:

0.418

Gnomad4 OTH exome

AF:

0.383

GnomAD4 genome

AF:

0.337

AC:

51212

AN:

152144

Hom.:

9959

Cov.:

AF XY:

0.339

AC XY:

25191

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.137

Gnomad4 AMR

AF:

0.383

Gnomad4 ASJ

AF:

0.297

Gnomad4 EAS

AF:

0.578

Gnomad4 SAS

AF:

0.467

Gnomad4 FIN

AF:

0.390

Gnomad4 NFE

AF:

0.414

Gnomad4 OTH

AF:

0.348

Alfa

AF:

0.375

Hom.:

3681

Bravo

AF:

0.326

Asia WGS

AF:

0.467

AC:

1626

AN:

3478

EpiCase

AF:

0.393

EpiControl

AF:

0.399

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

-0.52

CADD

Benign

4.8

DANN

Benign

0.72

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