rs148387796

Positions:

• chr12-40924536-CT-C
• chr12-40924536-CT-CTT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001843.4(CNTN1):​c.401-14del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00399 in 1,325,184 control chromosomes in the GnomAD database, including 14 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0028 (3 hom., cov: 29)
  • Exomes 𝑓: 0.0041 (11 hom.)
• Consequence: CNTN1 NM_001843.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.197

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 -16 ACMG points.

• BP6: Variant 12-40924536-CT-C is Benign according to our data. Variant chr12-40924536-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 258201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00284 (432/151910) while in subpopulation NFE AF= 0.0053 (360/67920). AF 95% confidence interval is 0.00485. There are 3 homozygotes in gnomad4. There are 183 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN1	NM_001843.4	c.401-14del		intron_variant		ENST00000551295.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN1	ENST00000551295.7	c.401-14del		intron_variant		1	NM_001843.4	P3

Frequencies

GnomAD3 genomes AF: 0.00285 AC: 432 AN: 151792 Hom.: 3 Cov.: 29

Gnomad AFR AF: 0.000750

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000756

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00530

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00252 AC: 595 AN: 236036 Hom.: 2 AF XY: 0.00240 AC XY: 305 AN XY: 127348

Gnomad AFR exome AF: 0.00124

Gnomad AMR exome AF: 0.00180

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000384

Gnomad FIN exome AF: 0.00138

Gnomad NFE exome AF: 0.00437

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00414 AC: 4861 AN: 1173274 Hom.: 11 Cov.: 16 AF XY: 0.00397 AC XY: 2375 AN XY: 597576

Gnomad4 AFR exome AF: 0.000831

Gnomad4 AMR exome AF: 0.00216

Gnomad4 ASJ exome AF: 0.0000415

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000468

Gnomad4 FIN exome AF: 0.00173

Gnomad4 NFE exome AF: 0.00522

Gnomad4 OTH exome AF: 0.00330

GnomAD4 genome AF: 0.00284 AC: 432 AN: 151910 Hom.: 3 Cov.: 29 AF XY: 0.00247 AC XY: 183 AN XY: 74230

Gnomad4 AFR AF: 0.000748

Gnomad4 AMR AF: 0.00177

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000756

Gnomad4 NFE AF: 0.00530

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00164 Hom.: 0

Bravo AF: 0.00289

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 26, 2018

- -

Compton-North congenital myopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

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: rs148387796; hg19: chr12-41318338;