12-40908622-A-G

Variant names:

• chr12-40908622-A-G
• rs75970534
• NM_001843.4:c.61+129A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

CNTN1 Gene-Disease associations (from GenCC):

• Compton-North congenital myopathy

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CNTN1	NM_001843.4	c.61+129A>G		intron_variant	Intron 2 of 23	ENST00000551295.7	NP_001834.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN1	ENST00000551295.7	c.61+129A>G		intron_variant	Intron 2 of 23	1	NM_001843.4	ENSP00000447006.1

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

African (AFR) AF: 0.0430 AC: 537 AN: 12496

American (AMR) AF: 0.235 AC: 4636 AN: 19746

Ashkenazi Jewish (ASJ) AF: 0.0624 AC: 913 AN: 14624

East Asian (EAS) AF: 0.167 AC: 4959 AN: 29656

South Asian (SAS) AF: 0.0336 AC: 1583 AN: 47132

European-Finnish (FIN) AF: 0.131 AC: 4016 AN: 30568

Middle Eastern (MID) AF: 0.0688 AC: 140 AN: 2036

European-Non Finnish (NFE) AF: 0.0435 AC: 12965 AN: 297810

Other (OTH) AF: 0.0606 AC: 1611 AN: 26596

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

African (AFR) AF: 0.0413 AC: 1717 AN: 41576

American (AMR) AF: 0.166 AC: 2536 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0634 AC: 220 AN: 3470

East Asian (EAS) AF: 0.147 AC: 760 AN: 5186

South Asian (SAS) AF: 0.0366 AC: 177 AN: 4830

European-Finnish (FIN) AF: 0.146 AC: 1549 AN: 10596

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0443 AC: 3012 AN: 68008

Other (OTH) AF: 0.0653 AC: 138 AN: 2112

Alfa AF: 0.0622 Hom.: 57

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

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		-1.4
PromoterAI		-0.0049	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs75970534; hg19: chr12-41302424;