rs10510173

Positions:

• chr3-1399227-T-A
• chr3-1399227-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001289080.2(CNTN6):​c.2705-2206T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 152,218 control chromosomes in the GnomAD database, including 57 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 0.022 (57 hom., cov: 33)
• Consequence: CNTN6 NM_001289080.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355

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=-0.82).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0222 (3377/152218) while in subpopulation SAS AF= 0.0545 (263/4830). AF 95% confidence interval is 0.049. There are 57 homozygotes in gnomad4. There are 1586 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 57 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN6	NM_001289080.2	c.2705-2206T>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.2705-2206T>A		intron_variant		1	NM_001289080.2	ENSP00000407822.2
CNTN6	ENST00000350110.2	c.2705-2206T>A		intron_variant		1		ENSP00000341882.2
CNTN6	ENST00000397479.6	n.*2843-2206T>A		intron_variant		2		ENSP00000380616.2

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3381 AN: 152100 Hom.: 57 Cov.: 33

Gnomad AFR AF: 0.00608

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0194

Gnomad ASJ AF: 0.0358

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.0544

Gnomad FIN AF: 0.00612

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0335

Gnomad OTH AF: 0.0321

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

GnomAD4 genome AF: 0.0222 AC: 3377 AN: 152218 Hom.: 57 Cov.: 33 AF XY: 0.0213 AC XY: 1586 AN XY: 74438

Gnomad4 AFR AF: 0.00604

Gnomad4 AMR AF: 0.0193

Gnomad4 ASJ AF: 0.0358

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.0545

Gnomad4 FIN AF: 0.00612

Gnomad4 NFE AF: 0.0335

Gnomad4 OTH AF: 0.0318

Alfa AF: 0.0140 Hom.: 2

Bravo AF: 0.0215

Asia WGS AF: 0.0160 AC: 59 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.63
DANN	Benign	0.65

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: rs10510173; hg19: chr3-1440911;