NM_001843.4:c.1416C>T

Variant names:

• chr12-40943633-C-T
• rs1056019
• NM_001843.4:c.1416C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001843.4(CNTN1):​c.1416C>T​(p.Asn472Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 1,591,976 control chromosomes in the GnomAD database, including 305,935 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (29423 hom., cov: 32)
  • Exomes 𝑓: 0.62 (276512 hom.)
• Consequence: CNTN1 NM_001843.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.557
• Publications: 23 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 12-40943633-C-T is Benign according to our data. Variant chr12-40943633-C-T is described in ClinVar as Benign. ClinVar VariationId is 128791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.557 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.65 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN1	NM_001843.4	MANE Select	c.1416C>T	p.Asn472Asn	synonymous	Exon 13 of 24	NP_001834.2
	CNTN1	NM_175038.2		c.1383C>T	p.Asn461Asn	synonymous	Exon 11 of 22	NP_778203.1
	CNTN1	NM_001256063.2		c.1416C>T	p.Asn472Asn	synonymous	Exon 13 of 16	NP_001242992.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN1	ENST00000551295.7	TSL:1 MANE Select	c.1416C>T	p.Asn472Asn	synonymous	Exon 13 of 24	ENSP00000447006.1
	CNTN1	ENST00000347616.5	TSL:1	c.1416C>T	p.Asn472Asn	synonymous	Exon 12 of 23	ENSP00000325660.3
	CNTN1	ENST00000348761.2	TSL:1	c.1383C>T	p.Asn461Asn	synonymous	Exon 11 of 22	ENSP00000261160.3

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94288 AN: 151734 Hom.: 29414 Cov.: 32

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.619

GnomAD2 exomes AF: 0.621 AC: 155177 AN: 249942 AF XY: 0.618

Gnomad AFR exome AF: 0.584

Gnomad AMR exome AF: 0.691

Gnomad ASJ exome AF: 0.666

Gnomad EAS exome AF: 0.462

Gnomad FIN exome AF: 0.683

Gnomad NFE exome AF: 0.636

Gnomad OTH exome AF: 0.638

GnomAD4 exome AF: 0.618 AC: 889684 AN: 1440126 Hom.: 276512 Cov.: 32 AF XY: 0.617 AC XY: 442770 AN XY: 717712

African (AFR) AF: 0.587 AC: 19388 AN: 33010

American (AMR) AF: 0.682 AC: 30436 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 17376 AN: 25934

East Asian (EAS) AF: 0.457 AC: 18041 AN: 39484

South Asian (SAS) AF: 0.542 AC: 46535 AN: 85784

European-Finnish (FIN) AF: 0.682 AC: 36371 AN: 53352

Middle Eastern (MID) AF: 0.696 AC: 3975 AN: 5710

European-Non Finnish (NFE) AF: 0.623 AC: 680753 AN: 1092580

Other (OTH) AF: 0.617 AC: 36809 AN: 59662

GnomAD4 genome AF: 0.621 AC: 94323 AN: 151850 Hom.: 29423 Cov.: 32 AF XY: 0.622 AC XY: 46118 AN XY: 74174

African (AFR) AF: 0.591 AC: 24484 AN: 41438

American (AMR) AF: 0.661 AC: 10041 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 2305 AN: 3472

East Asian (EAS) AF: 0.470 AC: 2432 AN: 5174

South Asian (SAS) AF: 0.550 AC: 2648 AN: 4818

European-Finnish (FIN) AF: 0.682 AC: 7177 AN: 10528

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.636 AC: 43169 AN: 67916

Other (OTH) AF: 0.611 AC: 1283 AN: 2100

Alfa AF: 0.630 Hom.: 58375

Bravo AF: 0.618

Asia WGS AF: 0.497 AC: 1727 AN: 3472

EpiCase AF: 0.640

EpiControl AF: 0.641

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Compton-North congenital myopathy (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.9
DANN	Benign	0.37
PhyloP100		-0.56
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1056019; hg19: chr12-41337435; COSMIC: COSV61637004;