rs10784981

Variant names:

• chr12-40980895-C-A
• rs10784981
• NM_001843.4:c.1805-14C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-40980895-C-A
• chr12-40980895-C-T

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.1805-14C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,611,240 control chromosomes in the GnomAD database, including 11,974 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1087 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10887 hom.)
• Consequence: CNTN1 NM_001843.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.289
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 12-40980895-C-A is Benign according to our data. Variant chr12-40980895-C-A is described in ClinVar as Benign. ClinVar VariationId is 258193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN1	NM_001843.4	c.1805-14C>A		intron_variant	Intron 15 of 23	ENST00000551295.7	NP_001834.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN1	ENST00000551295.7	c.1805-14C>A		intron_variant	Intron 15 of 23	1	NM_001843.4	ENSP00000447006.1
CNTN1	ENST00000347616.5	c.1805-14C>A		intron_variant	Intron 14 of 22	1		ENSP00000325660.3
CNTN1	ENST00000348761.2	c.1772-14C>A		intron_variant	Intron 13 of 21	1		ENSP00000261160.3

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17833 AN: 152078 Hom.: 1087 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0629

Gnomad SAS AF: 0.0726

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.112

GnomAD2 exomes AF: 0.111 AC: 27869 AN: 250562 AF XY: 0.111

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.104

Gnomad ASJ exome AF: 0.140

Gnomad EAS exome AF: 0.0651

Gnomad FIN exome AF: 0.153

Gnomad NFE exome AF: 0.121

Gnomad OTH exome AF: 0.117

GnomAD4 exome AF: 0.119 AC: 174091 AN: 1459044 Hom.: 10887 Cov.: 31 AF XY: 0.118 AC XY: 85710 AN XY: 726006

African (AFR) AF: 0.109 AC: 3632 AN: 33398

American (AMR) AF: 0.104 AC: 4631 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 3575 AN: 26088

East Asian (EAS) AF: 0.0517 AC: 2051 AN: 39668

South Asian (SAS) AF: 0.0766 AC: 6603 AN: 86212

European-Finnish (FIN) AF: 0.149 AC: 7942 AN: 53358

Middle Eastern (MID) AF: 0.110 AC: 629 AN: 5744

European-Non Finnish (NFE) AF: 0.124 AC: 137920 AN: 1109604

Other (OTH) AF: 0.118 AC: 7108 AN: 60290

GnomAD4 genome AF: 0.117 AC: 17839 AN: 152196 Hom.: 1087 Cov.: 32 AF XY: 0.117 AC XY: 8687 AN XY: 74422

African (AFR) AF: 0.110 AC: 4553 AN: 41536

American (AMR) AF: 0.116 AC: 1766 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 508 AN: 3466

East Asian (EAS) AF: 0.0624 AC: 323 AN: 5174

South Asian (SAS) AF: 0.0729 AC: 352 AN: 4828

European-Finnish (FIN) AF: 0.155 AC: 1644 AN: 10588

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8344 AN: 67998

Other (OTH) AF: 0.110 AC: 233 AN: 2110

Alfa AF: 0.0893 Hom.: 256

Bravo AF: 0.116

Asia WGS AF: 0.0780 AC: 270 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Feb 08, 2016

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.

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Compton-North congenital myopathy Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.7
DANN	Benign	0.59
PhyloP100		-0.29
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: rs10784981; hg19: chr12-41374697; COSMIC: COSV107424825; COSMIC: COSV107424825;