3-1356588-T-C

Variant summary

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

The NM_001289080.2(CNTN6):c.1492+4137T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 151,900 control chromosomes in the GnomAD database, including 127 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 0.034 (127 hom., cov: 32)
• Consequence: CNTN6 NM_001289080.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN6	NM_001289080.2	c.1492+4137T>C		intron_variant		ENST00000446702.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN6	ENST00000446702.7	c.1492+4137T>C		intron_variant		1	NM_001289080.2	P1
CNTN6	ENST00000350110.2	c.1492+4137T>C		intron_variant		1		P1
CNTN6	ENST00000397479.6	c.*1630+4137T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0345 AC: 5241 AN: 151782 Hom.: 127 Cov.: 32

Gnomad AFR AF: 0.00930

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0316

Gnomad ASJ AF: 0.0534

Gnomad EAS AF: 0.00583

Gnomad SAS AF: 0.0571

Gnomad FIN AF: 0.0464

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0481

Gnomad OTH AF: 0.0456

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

GnomAD4 genome AF: 0.0345 AC: 5239 AN: 151900 Hom.: 127 Cov.: 32 AF XY: 0.0344 AC XY: 2555 AN XY: 74240

Gnomad4 AFR AF: 0.00925

Gnomad4 AMR AF: 0.0315

Gnomad4 ASJ AF: 0.0534

Gnomad4 EAS AF: 0.00584

Gnomad4 SAS AF: 0.0572

Gnomad4 FIN AF: 0.0464

Gnomad4 NFE AF: 0.0482

Gnomad4 OTH AF: 0.0451

Alfa AF: 0.0429 Hom.: 16

Bravo AF: 0.0316

Asia WGS AF: 0.0210 AC: 73 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.0090
Dann	Benign	0.57

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: rs3772283; hg19: chr3-1398272;