chr12-40884141-C-T

Variant names:

• chr12-40884141-C-T
• rs7309734
• NM_001843.4:c.-76-24216C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001843.4(CNTN1):​c.-76-24216C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,286 control chromosomes in the GnomAD database, including 23,039 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (23039 hom., cov: 32)
• Consequence: CNTN1 NM_001843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.353
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 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.-76-24216C>T		intron	N/A	NP_001834.2
	CNTN1	NM_001256063.2		c.-76-24216C>T		intron	N/A	NP_001242992.1
	CNTN1	NM_001256064.2		c.-76-24216C>T		intron	N/A	NP_001242993.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN1	ENST00000551295.7	TSL:1 MANE Select	c.-76-24216C>T		intron	N/A	ENSP00000447006.1
	CNTN1	ENST00000547849.6	TSL:1	c.-76-24216C>T		intron	N/A	ENSP00000448653.1
	CNTN1	ENST00000547702.5	TSL:2	c.-76-24216C>T		intron	N/A	ENSP00000448004.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82301 AN: 151168 Hom.: 23023 Cov.: 32

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.533

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.544 AC: 82347 AN: 151286 Hom.: 23039 Cov.: 32 AF XY: 0.539 AC XY: 39881 AN XY: 73934

African (AFR) AF: 0.667 AC: 27609 AN: 41422

American (AMR) AF: 0.447 AC: 6786 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1858 AN: 3456

East Asian (EAS) AF: 0.295 AC: 1517 AN: 5148

South Asian (SAS) AF: 0.474 AC: 2283 AN: 4814

European-Finnish (FIN) AF: 0.504 AC: 5315 AN: 10542

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35273 AN: 67420

Other (OTH) AF: 0.527 AC: 1108 AN: 2102

Alfa AF: 0.526 Hom.: 10529

Bravo AF: 0.537

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.52
PhyloP100		-0.35
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: rs7309734; hg19: chr12-41277943;