12-40908572-A-C

Position:

• chr12-40908572-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.61+79A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0401 in 1,076,696 control chromosomes in the GnomAD database, including 1,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (112 hom., cov: 32)
  • Exomes 𝑓: 0.041 (928 hom.)
• Consequence: CNTN1 NM_001843.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0560

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=-0.81).
• BP6: Variant 12-40908572-A-C is Benign according to our data. Variant chr12-40908572-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 679918.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.075 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN1	NM_001843.4	c.61+79A>C		intron_variant		ENST00000551295.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN1	ENST00000551295.7	c.61+79A>C		intron_variant		1	NM_001843.4	P3

Frequencies

GnomAD3 genomes AF: 0.0334 AC: 5088 AN: 152206 Hom.: 112 Cov.: 32

Gnomad AFR AF: 0.00863

Gnomad AMI AF: 0.0857

Gnomad AMR AF: 0.0462

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.00634

Gnomad SAS AF: 0.0512

Gnomad FIN AF: 0.0210

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0463

Gnomad OTH AF: 0.0407

GnomAD4 exome AF: 0.0411 AC: 38030 AN: 924372 Hom.: 928 AF XY: 0.0420 AC XY: 19964 AN XY: 475114

Gnomad4 AFR exome AF: 0.00857

Gnomad4 AMR exome AF: 0.0505

Gnomad4 ASJ exome AF: 0.0544

Gnomad4 EAS exome AF: 0.00499

Gnomad4 SAS exome AF: 0.0527

Gnomad4 FIN exome AF: 0.0214

Gnomad4 NFE exome AF: 0.0432

Gnomad4 OTH exome AF: 0.0396

GnomAD4 genome AF: 0.0335 AC: 5096 AN: 152324 Hom.: 112 Cov.: 32 AF XY: 0.0336 AC XY: 2500 AN XY: 74476

Gnomad4 AFR AF: 0.00866

Gnomad4 AMR AF: 0.0462

Gnomad4 ASJ AF: 0.0501

Gnomad4 EAS AF: 0.00635

Gnomad4 SAS AF: 0.0522

Gnomad4 FIN AF: 0.0210

Gnomad4 NFE AF: 0.0463

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0399 Hom.: 17

Bravo AF: 0.0341

Asia WGS AF: 0.0270 AC: 92 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 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	-0.81
CADD	Benign	3.9
DANN	Benign	0.58

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: rs35684552; hg19: chr12-41302374;