3-1105517-A-G

Variant names:

• chr3-1105517-A-G
• rs6797539
• NM_001289080.2:c.-83+12397A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001289080.2(CNTN6):​c.-83+12397A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0646 in 152,252 control chromosomes in the GnomAD database, including 423 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 0.065 (423 hom., cov: 33)
• Consequence: CNTN6 NM_001289080.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.07
• Publications: 3 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN6	NM_001289080.2	c.-83+12397A>G		intron_variant	Intron 1 of 22	ENST00000446702.7	NP_001276009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN6	ENST00000446702.7	c.-83+12397A>G		intron_variant	Intron 1 of 22	1	NM_001289080.2	ENSP00000407822.2

Frequencies

GnomAD3 genomes AF: 0.0646 AC: 9830 AN: 152134 Hom.: 423 Cov.: 33

Gnomad AFR AF: 0.0246

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0618

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.00558

Gnomad SAS AF: 0.0809

Gnomad FIN AF: 0.0966

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0892

Gnomad OTH AF: 0.0507

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

GnomAD4 genome AF: 0.0646 AC: 9839 AN: 152252 Hom.: 423 Cov.: 33 AF XY: 0.0660 AC XY: 4914 AN XY: 74444

African (AFR) AF: 0.0246 AC: 1024 AN: 41566

American (AMR) AF: 0.0619 AC: 946 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0499 AC: 173 AN: 3468

East Asian (EAS) AF: 0.00540 AC: 28 AN: 5188

South Asian (SAS) AF: 0.0814 AC: 393 AN: 4830

European-Finnish (FIN) AF: 0.0966 AC: 1024 AN: 10604

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0892 AC: 6067 AN: 67990

Other (OTH) AF: 0.0501 AC: 106 AN: 2114

Alfa AF: 0.0849 Hom.: 289

Bravo AF: 0.0583

Asia WGS AF: 0.0380 AC: 133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.058
DANN	Benign	0.34
PhyloP100		-4.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6797539; hg19: chr3-1147201;