Genetic Variant CNTN4:c.-144-48723T>C (chr3-2290455-T-C) – 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.-144-48723T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 152,256 control chromosomes in the GnomAD database, including 61,609 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.90 ( 61609 hom., cov: 33)

Consequence

CNTN4
NM_175607.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0210

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):

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

CNTN4 links:

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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=-1.01).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175607.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CNTN4	NM_175607.3	MANE Select	c.-144-48723T>C	intron	N/A	NP_783200.1	Q8IWV2-1
CNTN4	NM_001206955.2		c.-144-48723T>C	intron	N/A	NP_001193884.1	Q8IWV2-1
CNTN4	NM_001350095.2		c.-144-48723T>C	intron	N/A	NP_001337024.1	Q8IWV2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CNTN4	ENST00000418658.6	TSL:5 MANE Select	c.-144-48723T>C	intron	N/A	ENSP00000396010.1	Q8IWV2-1
CNTN4	ENST00000397461.5	TSL:5	c.-144-48723T>C	intron	N/A	ENSP00000380602.1	Q8IWV2-1
CNTN4	ENST00000422330.5	TSL:4	c.-144-48723T>C	intron	N/A	ENSP00000408594.1	C9JMQ2

Frequencies

GnomAD3 genomes

AF:

0.899

AC:

136753

AN:

152138

Hom.:

61538

Cov.:

show subpopulations

Gnomad AFR

AF:

0.937

Gnomad AMI

AF:

0.907

Gnomad AMR

AF:

0.922

Gnomad ASJ

AF:

0.892

Gnomad EAS

AF:

0.960

Gnomad SAS

AF:

0.927

Gnomad FIN

AF:

0.864

Gnomad MID

AF:

0.902

Gnomad NFE

AF:

0.870

Gnomad OTH

AF:

0.886

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

GnomAD4 genome

AF:

0.899

AC:

136884

AN:

152256

Hom.:

61609

Cov.:

AF XY:

0.900

AC XY:

66976

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.937

AC:

38917

AN:

41546

American (AMR)

AF:

0.922

AC:

14097

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.892

AC:

3094

AN:

3470

East Asian (EAS)

AF:

0.960

AC:

4966

AN:

5174

South Asian (SAS)

AF:

0.927

AC:

4472

AN:

4822

European-Finnish (FIN)

AF:

0.864

AC:

9161

AN:

10608

Middle Eastern (MID)

AF:

0.908

AC:

267

AN:

294

European-Non Finnish (NFE)

AF:

0.870

AC:

59203

AN:

68022

Other (OTH)

AF:

0.888

AC:

1880

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

716

1432

2148

2864

3580

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

902

1804

2706

3608

4510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.877

Hom.:

86464

Bravo

AF:

0.904

Asia WGS

AF:

0.935

AC:

3251

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.9

(source)

DANN

Benign

0.39

PhyloP100

-0.021

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over