12-40910023-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001843.4(CNTN1):c.62-50A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,376,668 control chromosomes in the GnomAD database, including 58,353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4978 hom., cov: 32)
  • Exomes 𝑓: 0.29 (53375 hom.)
• Consequence: CNTN1 NM_001843.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.645

Genes affected

CNTN1 (HGNC:2171): (contactin 1) 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. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 12-40910023-A-C is Benign according to our data. Variant chr12-40910023-A-C is described in ClinVar as [Benign]. Clinvar id is 680155.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN1	NM_001843.4	c.62-50A>C		intron_variant		ENST00000551295.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN1	ENST00000551295.7	c.62-50A>C		intron_variant		1	NM_001843.4	P3

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36353 AN: 151904 Hom.: 4988 Cov.: 32

Gnomad AFR AF: 0.0993

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.270

GnomAD3 exomes AF: 0.270 AC: 67223 AN: 248762 Hom.: 9943 AF XY: 0.281 AC XY: 37891 AN XY: 134670

Gnomad AFR exome AF: 0.0921

Gnomad AMR exome AF: 0.158

Gnomad ASJ exome AF: 0.365

Gnomad EAS exome AF: 0.224

Gnomad SAS exome AF: 0.320

Gnomad FIN exome AF: 0.259

Gnomad NFE exome AF: 0.316

Gnomad OTH exome AF: 0.300

GnomAD4 exome AF: 0.291 AC: 356110 AN: 1224646 Hom.: 53375 Cov.: 17 AF XY: 0.295 AC XY: 183068 AN XY: 621364

Gnomad4 AFR exome AF: 0.0935

Gnomad4 AMR exome AF: 0.165

Gnomad4 ASJ exome AF: 0.370

Gnomad4 EAS exome AF: 0.203

Gnomad4 SAS exome AF: 0.320

Gnomad4 FIN exome AF: 0.270

Gnomad4 NFE exome AF: 0.303

Gnomad4 OTH exome AF: 0.293

GnomAD4 genome AF: 0.239 AC: 36334 AN: 152022 Hom.: 4978 Cov.: 32 AF XY: 0.238 AC XY: 17720 AN XY: 74330

Gnomad4 AFR AF: 0.0991

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.267

Alfa AF: 0.289 Hom.: 2047

Bravo AF: 0.225

Asia WGS AF: 0.248 AC: 860 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	7.1
Dann	Benign	0.69

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: rs2304819; hg19: chr12-41303825; COSMIC: COSV61636349;