chr12-40924536-CT-C

Variant names:

• chr12-40924536-CT-C
• rs148387796
• NM_001843.4:c.401-14delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001843.4(CNTN1):​c.401-14delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00399 in 1,325,184 control chromosomes in the GnomAD database, including 14 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0028 (3 hom., cov: 29)
  • Exomes 𝑓: 0.0041 (11 hom.)
• Consequence: CNTN1 NM_001843.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.197
• Publications: 0 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 -16 ACMG points.

• BP6: Variant 12-40924536-CT-C is Benign according to our data. Variant chr12-40924536-CT-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00284 (432/151910) while in subpopulation NFE AF = 0.0053 (360/67920). AF 95% confidence interval is 0.00485. There are 3 homozygotes in GnomAd4. There are 183 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR,Unknown gene

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.401-14delT		intron	N/A	NP_001834.2
	CNTN1	NM_175038.2		c.368-14delT		intron	N/A	NP_778203.1	Q12860-2
	CNTN1	NM_001256063.2		c.401-14delT		intron	N/A	NP_001242992.1	Q12860-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN1	ENST00000551295.7	TSL:1 MANE Select	c.401-20delT		intron	N/A	ENSP00000447006.1	Q12860-1
	CNTN1	ENST00000347616.5	TSL:1	c.401-20delT		intron	N/A	ENSP00000325660.3	Q12860-1
	CNTN1	ENST00000348761.2	TSL:1	c.368-20delT		intron	N/A	ENSP00000261160.3	Q12860-2

Frequencies

GnomAD3 genomes AF: 0.00285 AC: 432 AN: 151792 Hom.: 3 Cov.: 29

Gnomad AFR AF: 0.000750

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000756

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00530

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00252 AC: 595 AN: 236036 AF XY: 0.00240

Gnomad AFR exome AF: 0.00124

Gnomad AMR exome AF: 0.00180

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00138

Gnomad NFE exome AF: 0.00437

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00414 AC: 4861 AN: 1173274 Hom.: 11 Cov.: 16 AF XY: 0.00397 AC XY: 2375 AN XY: 597576

African (AFR) AF: 0.000831 AC: 23 AN: 27664

American (AMR) AF: 0.00216 AC: 94 AN: 43458

Ashkenazi Jewish (ASJ) AF: 0.0000415 AC: 1 AN: 24112

East Asian (EAS) AF: 0.00 AC: 0 AN: 37912

South Asian (SAS) AF: 0.000468 AC: 37 AN: 79042

European-Finnish (FIN) AF: 0.00173 AC: 91 AN: 52670

Middle Eastern (MID) AF: 0.000192 AC: 1 AN: 5198

European-Non Finnish (NFE) AF: 0.00522 AC: 4447 AN: 852658

Other (OTH) AF: 0.00330 AC: 167 AN: 50560

GnomAD4 genome AF: 0.00284 AC: 432 AN: 151910 Hom.: 3 Cov.: 29 AF XY: 0.00247 AC XY: 183 AN XY: 74230

African (AFR) AF: 0.000748 AC: 31 AN: 41432

American (AMR) AF: 0.00177 AC: 27 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.000756 AC: 8 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00530 AC: 360 AN: 67920

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00164 Hom.: 0

Bravo AF: 0.00289

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism

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: rs148387796; hg19: chr12-41318338; COSMIC: COSV100750862; COSMIC: COSV100750862;