Genetic Variant CNTN6:c.2705-2206T>A (chr3-1399227-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001289080.2(CNTN6):c.2705-2206T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 152,218 control chromosomes in the GnomAD database, including 57 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 0.022 ( 57 hom., cov: 33)

Consequence

CNTN6
NM_001289080.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.355

Publications

0 publications found

Variant links:

Genes affected

CNTN6 (HGNC:2176): (contactin 6) The protein encoded by this gene is a member of the immunoglobulin superfamily. It is a glycosylphosphatidylinositol (GPI)-anchored neuronal membrane protein that functions as a cell adhesion molecule. It may play a role in the formation of axon connections in the developing nervous system. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

CNTN6 Gene-Disease associations (from GenCC):

Tourette syndrome
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
complex neurodevelopmental disorder
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

CNTN6 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=-0.82).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0222 (3377/152218) while in subpopulation SAS AF = 0.0545 (263/4830). AF 95% confidence interval is 0.049. There are 57 homozygotes in GnomAd4. There are 1586 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 3377 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN6	NM_001289080.2 link	c.2705-2206T>A		intron_variant	Intron 20 of 22	ENST00000446702.7	NP_001276009.1	Q9UQ52A1LMA8B4DGV0

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CNTN6	ENST00000446702.7 link	c.2705-2206T>A	intron_variant	Intron 20 of 22	1	NM_001289080.2	ENSP00000407822.2	Q9UQ52
CNTN6	ENST00000350110.2 link	c.2705-2206T>A	intron_variant	Intron 20 of 22	1		ENSP00000341882.2	Q9UQ52
CNTN6	ENST00000397479.6 link	n.*2843-2206T>A	intron_variant	Intron 19 of 21	2		ENSP00000380616.2	F8VWS7

Frequencies

GnomAD3 genomes

AF:

0.0222

AC:

3381

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00608

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0194

Gnomad ASJ

AF:

0.0358

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.0544

Gnomad FIN

AF:

0.00612

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0335

Gnomad OTH

AF:

0.0321

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

GnomAD4 genome

AF:

0.0222

AC:

3377

AN:

152218

Hom.:

Cov.:

AF XY:

0.0213

AC XY:

1586

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.00604

AC:

251

AN:

41558

American (AMR)

AF:

0.0193

AC:

295

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0358

AC:

124

AN:

3468

East Asian (EAS)

AF:

0.00270

AC:

AN:

5176

South Asian (SAS)

AF:

0.0545

AC:

263

AN:

4830

European-Finnish (FIN)

AF:

0.00612

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0335

AC:

2278

AN:

67974

Other (OTH)

AF:

0.0318

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

171

342

512

683

854

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0140

Hom.:

Bravo

AF:

0.0215

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.63

(source)

DANN

Benign

0.65

PhyloP100

-0.35

Mutation Taster

=100/0

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over