rs6442221

Positions:

• chr3-1130176-G-A
• chr3-1130176-G-C
• chr3-1130176-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN6	NM_001289080.2	c.-82-17751G>A		intron_variant		ENST00000446702.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN6	ENST00000446702.7	c.-82-17751G>A		intron_variant		1	NM_001289080.2	P1

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

Gnomad4 AFR AF: 0.849

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.651

Gnomad4 EAS AF: 0.482

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.615

Gnomad4 OTH AF: 0.677

Alfa AF: 0.629 Hom.: 11989

Bravo AF: 0.684

Asia WGS AF: 0.518 AC: 1803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.51

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: rs6442221; hg19: chr3-1171860;