rs12367345

Variant names:

• chr12-41027840-A-G
• rs12367345
• NM_001843.4:c.2711-17A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001843.4(CNTN1):​c.2711-17A>G variant causes a 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 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.547
• Publications: 4 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), Orphanet, Ambry Genetics
• schizophrenia

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001843.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN1	NM_001843.4	MANE Select	c.2711-17A>G		intron	N/A	NP_001834.2
	CNTN1	NM_175038.2		c.2678-17A>G		intron	N/A	NP_778203.1	Q12860-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN1	ENST00000551295.7	TSL:1 MANE Select	c.2711-17A>G		intron	N/A	ENSP00000447006.1	Q12860-1
	CNTN1	ENST00000347616.5	TSL:1	c.2711-17A>G		intron	N/A	ENSP00000325660.3	Q12860-1
	CNTN1	ENST00000348761.2	TSL:1	c.2678-17A>G		intron	N/A	ENSP00000261160.3	Q12860-2

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

GnomAD2 exomes AF: 0.128 AC: 32092 AN: 250542 AF XY: 0.129

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 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

African (AFR) AF: 0.0518 AC: 1601 AN: 30926

American (AMR) AF: 0.110 AC: 4880 AN: 44500

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 2819 AN: 25396

East Asian (EAS) AF: 0.0571 AC: 2231 AN: 39060

South Asian (SAS) AF: 0.0811 AC: 6791 AN: 83732

European-Finnish (FIN) AF: 0.186 AC: 9900 AN: 53304

Middle Eastern (MID) AF: 0.110 AC: 609 AN: 5520

European-Non Finnish (NFE) AF: 0.160 AC: 160514 AN: 1001360

Other (OTH) AF: 0.136 AC: 7640 AN: 56228

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

African (AFR) AF: 0.0542 AC: 2252 AN: 41534

American (AMR) AF: 0.117 AC: 1785 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 401 AN: 3470

East Asian (EAS) AF: 0.0717 AC: 371 AN: 5172

South Asian (SAS) AF: 0.0790 AC: 381 AN: 4824

European-Finnish (FIN) AF: 0.195 AC: 2067 AN: 10574

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10663 AN: 67974

Other (OTH) AF: 0.123 AC: 260 AN: 2114

Alfa AF: 0.128 Hom.: 1262

Bravo AF: 0.113

Asia WGS AF: 0.0750 AC: 260 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Compton-North congenital myopathy (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.021
DANN	Benign	0.64
PhyloP100		-0.55
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: rs12367345; hg19: chr12-41421642; COSMIC: COSV61645323; COSMIC: COSV61645323;