rs9815195

Positions:

• chr3-1259446-C-A
• chr3-1259446-C-T

Variant summary

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

The ENST00000446702.7(CNTN6):​c.359-18967C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 151,840 control chromosomes in the GnomAD database, including 7,937 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 0.29 (7937 hom., cov: 33)
• Consequence: CNTN6 ENST00000446702.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.877

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN6	NM_001289080.2	c.359-18967C>A		intron_variant		ENST00000446702.7	NP_001276009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN6	ENST00000446702.7	c.359-18967C>A		intron_variant		1	NM_001289080.2	ENSP00000407822	P1
CNTN6	ENST00000350110.2	c.359-18967C>A		intron_variant		1		ENSP00000341882	P1
CNTN6	ENST00000394261.2	c.*337-18967C>A		intron_variant, NMD_transcript_variant		1		ENSP00000377804
CNTN6	ENST00000397479.6	c.*497-18967C>A		intron_variant, NMD_transcript_variant		2		ENSP00000380616

Frequencies

GnomAD3 genomes AF: 0.290 AC: 43985 AN: 151722 Hom.: 7900 Cov.: 33

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.290 AC: 44072 AN: 151840 Hom.: 7937 Cov.: 33 AF XY: 0.286 AC XY: 21192 AN XY: 74218

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.254

Alfa AF: 0.219 Hom.: 1498

Bravo AF: 0.307

Asia WGS AF: 0.193 AC: 672 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.1
DANN	Benign	0.44

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: rs9815195; hg19: chr3-1301130; COSMIC: COSV63174444;