Genetic Variant CNTN4:c.55+61947C>T (chr3-2633505-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_175607.3(CNTN4):c.55+61947C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,120 control chromosomes in the GnomAD database, including 5,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (★).

Frequency

Genomes: 𝑓 0.25 ( 5573 hom., cov: 33)

Consequence

CNTN4
NM_175607.3 intron

Scores

Clinical Significance

association criteria provided, single submitter O:1

Conservation

PhyloP100: -0.771

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
autism spectrum disorder
Inheritance: AD Classification: NO_KNOWN Submitted by: Illumina

CNTN4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN4	NM_175607.3 link	c.55+61947C>T		intron_variant	Intron 4 of 24	ENST00000418658.6	NP_783200.1	Q8IWV2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6 link	c.55+61947C>T		intron_variant	Intron 4 of 24	5	NM_175607.3	ENSP00000396010.1		Q8IWV2-1

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37630

AN:

152000

Hom.:

5556

Cov.:

show subpopulations

Gnomad AFR

AF:

0.410

Gnomad AMI

AF:

0.114

Gnomad AMR

AF:

0.283

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.0892

Gnomad SAS

AF:

0.235

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.159

Gnomad NFE

AF:

0.171

Gnomad OTH

AF:

0.221

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.248

AC:

37704

AN:

152120

Hom.:

5573

Cov.:

AF XY:

0.249

AC XY:

18530

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.411

AC:

17039

AN:

41474

American (AMR)

AF:

0.284

AC:

4340

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

475

AN:

3468

East Asian (EAS)

AF:

0.0889

AC:

461

AN:

5188

South Asian (SAS)

AF:

0.234

AC:

1125

AN:

4814

European-Finnish (FIN)

AF:

0.190

AC:

2006

AN:

10574

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.171

AC:

11638

AN:

67994

Other (OTH)

AF:

0.222

AC:

469

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1391

2782

4174

5565

6956

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.192

Hom.:

14132

Bravo

AF:

0.258

Asia WGS

AF:

0.202

AC:

703

AN:

3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Lip and oral cavity carcinoma

Other:1

Jan 01, 2016

Department of Biological Science, Sunandan Divatia School of Science, NMIMS University

Significance:association

Review Status:criteria provided, single submitter

Collection Method:case-control

The homozygous WT (CC) genotype showed a higher frequency in cases as compared to controls and a significant association was observed with an OR of 1.41 (1.09-1.82). The heterozygous genotype indicated decreased risk to oral cancer with an OR 0.75 (0.58-0.97) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.21

(source)

DANN

Benign

0.66

PhyloP100

-0.77

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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3-2633505-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over