rs12367345

Positions:

• chr12-41027840-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001843.4(CNTN1):​c.2711-17A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,492,160 control chromosomes in the GnomAD database, including 16,623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1290 hom., cov: 32)
  • Exomes 𝑓: 0.15 (15333 hom.)
• Consequence: CNTN1 NM_001843.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.547

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 12-41027840-A-G is Benign according to our data. Variant chr12-41027840-A-G is described in ClinVar as [Benign]. Clinvar id is 258196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN1	NM_001843.4	c.2711-17A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000551295.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN1	ENST00000551295.7	c.2711-17A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001843.4	P3
CNTN1	ENST00000347616.5	c.2711-17A>G		splice_polypyrimidine_tract_variant, intron_variant		1		P3
CNTN1	ENST00000348761.2	c.2678-17A>G		splice_polypyrimidine_tract_variant, intron_variant		1		A1
CNTN1	ENST00000550305.1	n.670-17A>G		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18308 AN: 152016 Hom.: 1289 Cov.: 32

Gnomad AFR AF: 0.0543

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0720

Gnomad SAS AF: 0.0789

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.124

GnomAD3 exomes AF: 0.128 AC: 32092 AN: 250542 Hom.: 2301 AF XY: 0.129 AC XY: 17464 AN XY: 135402

Gnomad AFR exome AF: 0.0521

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.112

Gnomad EAS exome AF: 0.0750

Gnomad SAS exome AF: 0.0775

Gnomad FIN exome AF: 0.190

Gnomad NFE exome AF: 0.156

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.147 AC: 196985 AN: 1340026 Hom.: 15333 Cov.: 22 AF XY: 0.145 AC XY: 97783 AN XY: 673624

Gnomad4 AFR exome AF: 0.0518

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.111

Gnomad4 EAS exome AF: 0.0571

Gnomad4 SAS exome AF: 0.0811

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.136

GnomAD4 genome AF: 0.120 AC: 18308 AN: 152134 Hom.: 1290 Cov.: 32 AF XY: 0.120 AC XY: 8957 AN XY: 74360

Gnomad4 AFR AF: 0.0542

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.0717

Gnomad4 SAS AF: 0.0790

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.123

Alfa AF: 0.140 Hom.: 961

Bravo AF: 0.113

Asia WGS AF: 0.0750 AC: 260 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 08, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Compton-North congenital myopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.021
DANN	Benign	0.64

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: rs12367345; hg19: chr12-41421642; COSMIC: COSV61645323; COSMIC: COSV61645323;