rs201396853

chr12-40922441-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_001843.4(CNTN1):c.400+13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,613,438 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (2 hom.)
• Consequence: CNTN1 NM_001843.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.464

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 12-40922441-T-C is Benign according to our data. Variant chr12-40922441-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 258200.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 = 0.00104 (159/152256) while in subpopulation NFE AF= 0.00198 (135/68014). AF 95% confidence interval is 0.00171. There are 0 homozygotes in gnomad4. There are 75 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN1	NM_001843.4	c.400+13T>C		intron_variant		ENST00000551295.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN1	ENST00000551295.7	c.400+13T>C		intron_variant		1	NM_001843.4	P3

Frequencies

GnomAD3 genomes AF: 0.00105 AC: 159 AN: 152138 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00198

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.000924 AC: 232 AN: 250950 Hom.: 0 AF XY: 0.000943 AC XY: 128 AN XY: 135672

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000608

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00174

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.00123 AC: 1794 AN: 1461182 Hom.: 2 Cov.: 31 AF XY: 0.00119 AC XY: 862 AN XY: 726894

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.000492

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.000281

Gnomad4 NFE exome AF: 0.00151

Gnomad4 OTH exome AF: 0.000977

GnomAD4 genome AF: 0.00104 AC: 159 AN: 152256 Hom.: 0 Cov.: 32 AF XY: 0.00101 AC XY: 75 AN XY: 74434

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00198

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00161 Hom.: 0

Bravo AF: 0.000956

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 03, 2017	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. -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Compton-North congenital myopathy Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Sep 20, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 28, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	3.7
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201396853; hg19: chr12-41316243;