rs312274

Variant names:

• chr12-40852478-T-A
• rs312274
• NM_001843.4:c.-76-55879T>A

Your query was ambiguous. Multiple possible variants found:

• chr12-40852478-T-A
• chr12-40852478-T-C

Variant summary

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

The NM_001843.4(CNTN1):​c.-76-55879T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,004 control chromosomes in the GnomAD database, including 4,735 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 0.24 (4735 hom., cov: 31)
• Consequence: CNTN1 NM_001843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN1	NM_001843.4	c.-76-55879T>A		intron_variant	Intron 1 of 23	ENST00000551295.7	NP_001834.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN1	ENST00000551295.7	c.-76-55879T>A		intron_variant	Intron 1 of 23	1	NM_001843.4	ENSP00000447006.1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35999 AN: 151886 Hom.: 4741 Cov.: 31

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.237 AC: 35984 AN: 152004 Hom.: 4735 Cov.: 31 AF XY: 0.236 AC XY: 17570 AN XY: 74292

African (AFR) AF: 0.120 AC: 4984 AN: 41488

American (AMR) AF: 0.224 AC: 3424 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1177 AN: 3466

East Asian (EAS) AF: 0.211 AC: 1089 AN: 5156

South Asian (SAS) AF: 0.350 AC: 1684 AN: 4812

European-Finnish (FIN) AF: 0.246 AC: 2604 AN: 10572

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20126 AN: 67936

Other (OTH) AF: 0.264 AC: 557 AN: 2110

Alfa AF: 0.140 Hom.: 271

Bravo AF: 0.224

Asia WGS AF: 0.266 AC: 926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.74
PhyloP100		-1.4
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: rs312274; hg19: chr12-41246280;