NM_001843.4:c.1014T>C

Variant names:

• chr12-40936809-T-C
• rs935105
• NM_001843.4:c.1014T>C

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.1014T>C​(p.Asn338Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,612,934 control chromosomes in the GnomAD database, including 12,701 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1453 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11248 hom.)
• Consequence: CNTN1 NM_001843.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.171
• Publications: 14 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 12-40936809-T-C is Benign according to our data. Variant chr12-40936809-T-C is described in ClinVar as Benign. ClinVar VariationId is 128790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.171 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 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.1014T>C	p.Asn338Asn	synonymous	Exon 10 of 24	NP_001834.2
	CNTN1	NM_175038.2		c.981T>C	p.Asn327Asn	synonymous	Exon 8 of 22	NP_778203.1	Q12860-2
	CNTN1	NM_001256063.2		c.1014T>C	p.Asn338Asn	synonymous	Exon 10 of 16	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.1014T>C	p.Asn338Asn	synonymous	Exon 10 of 24	ENSP00000447006.1	Q12860-1
	CNTN1	ENST00000347616.5	TSL:1	c.1014T>C	p.Asn338Asn	synonymous	Exon 9 of 23	ENSP00000325660.3	Q12860-1
	CNTN1	ENST00000348761.2	TSL:1	c.981T>C	p.Asn327Asn	synonymous	Exon 8 of 22	ENSP00000261160.3	Q12860-2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20497 AN: 152042 Hom.: 1454 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.0628

Gnomad SAS AF: 0.0731

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.129

GnomAD2 exomes AF: 0.116 AC: 29040 AN: 250680 AF XY: 0.114

Gnomad AFR exome AF: 0.169

Gnomad AMR exome AF: 0.107

Gnomad ASJ exome AF: 0.140

Gnomad EAS exome AF: 0.0655

Gnomad FIN exome AF: 0.153

Gnomad NFE exome AF: 0.121

Gnomad OTH exome AF: 0.120

GnomAD4 exome AF: 0.121 AC: 177446 AN: 1460774 Hom.: 11248 Cov.: 34 AF XY: 0.120 AC XY: 87103 AN XY: 726676

African (AFR) AF: 0.171 AC: 5706 AN: 33432

American (AMR) AF: 0.107 AC: 4766 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 3592 AN: 26096

East Asian (EAS) AF: 0.0515 AC: 2042 AN: 39682

South Asian (SAS) AF: 0.0763 AC: 6585 AN: 86248

European-Finnish (FIN) AF: 0.149 AC: 7936 AN: 53396

Middle Eastern (MID) AF: 0.113 AC: 650 AN: 5758

European-Non Finnish (NFE) AF: 0.125 AC: 138791 AN: 1111180

Other (OTH) AF: 0.122 AC: 7378 AN: 60322

GnomAD4 genome AF: 0.135 AC: 20512 AN: 152160 Hom.: 1453 Cov.: 32 AF XY: 0.134 AC XY: 9994 AN XY: 74400

African (AFR) AF: 0.171 AC: 7097 AN: 41504

American (AMR) AF: 0.122 AC: 1862 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 508 AN: 3468

East Asian (EAS) AF: 0.0624 AC: 323 AN: 5180

South Asian (SAS) AF: 0.0734 AC: 354 AN: 4826

European-Finnish (FIN) AF: 0.154 AC: 1633 AN: 10592

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8349 AN: 68008

Other (OTH) AF: 0.127 AC: 269 AN: 2110

Alfa AF: 0.127 Hom.: 969

Bravo AF: 0.136

Asia WGS AF: 0.0810 AC: 281 AN: 3478

EpiCase AF: 0.120

EpiControl AF: 0.122

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	5.9
DANN	Benign	0.65
PhyloP100		0.17
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: rs935105; hg19: chr12-41330611; COSMIC: COSV61645756;