3-1268727-C-T

Position:

• chr3-1268727-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001289080.2(CNTN6):​c.359-9686C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 151,742 control chromosomes in the GnomAD database, including 23,142 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 0.54 (23142 hom., cov: 31)
• Consequence: CNTN6 NM_001289080.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.979

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN6	NM_001289080.2	c.359-9686C>T		intron_variant		ENST00000446702.7	NP_001276009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN6	ENST00000446702.7	c.359-9686C>T		intron_variant		1	NM_001289080.2	ENSP00000407822.2
CNTN6	ENST00000350110.2	c.359-9686C>T		intron_variant		1		ENSP00000341882.2
CNTN6	ENST00000394261.2	n.*337-9686C>T		intron_variant		1		ENSP00000377804.2
CNTN6	ENST00000397479.6	n.*497-9686C>T		intron_variant		2		ENSP00000380616.2

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81642 AN: 151626 Hom.: 23092 Cov.: 31

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.539 AC: 81746 AN: 151742 Hom.: 23142 Cov.: 31 AF XY: 0.546 AC XY: 40515 AN XY: 74150

Gnomad4 AFR AF: 0.654

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.823

Gnomad4 SAS AF: 0.704

Gnomad4 FIN AF: 0.489

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.525

Alfa AF: 0.481 Hom.: 4068

Bravo AF: 0.552

Asia WGS AF: 0.755 AC: 2625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.7
DANN	Benign	0.53

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

LitVar

Other links and lift over

dbSNP: rs9835344; hg19: chr3-1310411;