3-1130176-G-A

Variant names:

• chr3-1130176-G-A
• rs6442221
• NM_001289080.2:c.-82-17751G>A

Variant summary

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

The NM_001289080.2(CNTN6):​c.-82-17751G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 151,838 control chromosomes in the GnomAD database, including 36,078 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 0.68 (36078 hom., cov: 31)
• Consequence: CNTN6 NM_001289080.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.529
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001289080.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN6	NM_001289080.2	MANE Select	c.-82-17751G>A		intron	N/A	NP_001276009.1	Q9UQ52
	CNTN6	NM_001349350.2		c.-83+1799G>A		intron	N/A	NP_001336279.1	Q9UQ52
	CNTN6	NM_001349351.2		c.-83+1799G>A		intron	N/A	NP_001336280.1	Q9UQ52

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN6	ENST00000446702.7	TSL:1 MANE Select	c.-82-17751G>A		intron	N/A	ENSP00000407822.2	Q9UQ52
	CNTN6	ENST00000350110.2	TSL:1	c.-82-17751G>A		intron	N/A	ENSP00000341882.2	Q9UQ52
	CNTN6	ENST00000394261.2	TSL:1	n.-93-17751G>A		intron	N/A	ENSP00000377804.2	F8WDQ0

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103029 AN: 151720 Hom.: 36035 Cov.: 31

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.679

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

GnomAD4 genome AF: 0.679 AC: 103127 AN: 151838 Hom.: 36078 Cov.: 31 AF XY: 0.680 AC XY: 50458 AN XY: 74194

African (AFR) AF: 0.849 AC: 35210 AN: 41482

American (AMR) AF: 0.635 AC: 9654 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2256 AN: 3468

East Asian (EAS) AF: 0.482 AC: 2474 AN: 5130

South Asian (SAS) AF: 0.540 AC: 2598 AN: 4812

European-Finnish (FIN) AF: 0.657 AC: 6947 AN: 10570

Middle Eastern (MID) AF: 0.661 AC: 193 AN: 292

European-Non Finnish (NFE) AF: 0.615 AC: 41736 AN: 67864

Other (OTH) AF: 0.677 AC: 1425 AN: 2106

Alfa AF: 0.630 Hom.: 13789

Bravo AF: 0.684

Asia WGS AF: 0.518 AC: 1803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.51
PhyloP100		0.53
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: rs6442221; hg19: chr3-1171860;