12-40908622-A-G

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+129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0656 in 632,948 control chromosomes in the GnomAD database, including 2,424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.067 (551 hom., cov: 32)
  • Exomes 𝑓: 0.065 (1873 hom.)
• Consequence: CNTN1 NM_001843.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.43

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 12-40908622-A-G is Benign according to our data. Variant chr12-40908622-A-G is described in ClinVar as [Benign]. Clinvar id is 680305.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN1	NM_001843.4	c.61+129A>G		intron_variant		ENST00000551295.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN1	ENST00000551295.7	c.61+129A>G		intron_variant		1	NM_001843.4	P3

Frequencies

GnomAD3 genomes AF: 0.0668 AC: 10162 AN: 152166 Hom.: 546 Cov.: 32

Gnomad AFR AF: 0.0413

Gnomad AMI AF: 0.0505

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.0368

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0443

Gnomad OTH AF: 0.0660

GnomAD4 exome AF: 0.0652 AC: 31360 AN: 480664 Hom.: 1873 AF XY: 0.0621 AC XY: 15872 AN XY: 255714

Gnomad4 AFR exome AF: 0.0430

Gnomad4 AMR exome AF: 0.235

Gnomad4 ASJ exome AF: 0.0624

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.0336

Gnomad4 FIN exome AF: 0.131

Gnomad4 NFE exome AF: 0.0435

Gnomad4 OTH exome AF: 0.0606

GnomAD4 genome AF: 0.0668 AC: 10171 AN: 152284 Hom.: 551 Cov.: 32 AF XY: 0.0732 AC XY: 5448 AN XY: 74462

Gnomad4 AFR AF: 0.0413

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.0634

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.0366

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.0443

Gnomad4 OTH AF: 0.0653

Alfa AF: 0.0629 Hom.: 56

Bravo AF: 0.0727

Asia WGS AF: 0.0790 AC: 275 AN: 3478

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 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	-0.86
Cadd	Benign	0.21
Dann	Benign	0.48

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: rs75970534; hg19: chr12-41302424;