rs278917

Variant names:

• chr12-40986686-A-C
• rs278917
• NM_001843.4:c.1963+5619A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-40986686-A-C
• chr12-40986686-A-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.1963+5619A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 151,886 control chromosomes in the GnomAD database, including 27,868 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 0.60 (27868 hom., cov: 31)
• Consequence: CNTN1 NM_001843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN1	NM_001843.4	c.1963+5619A>C		intron_variant	Intron 16 of 23	ENST00000551295.7	NP_001834.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN1	ENST00000551295.7	c.1963+5619A>C		intron_variant	Intron 16 of 23	1	NM_001843.4	ENSP00000447006.1
CNTN1	ENST00000347616.5	c.1963+5619A>C		intron_variant	Intron 15 of 22	1		ENSP00000325660.3
CNTN1	ENST00000348761.2	c.1930+5619A>C		intron_variant	Intron 14 of 21	1		ENSP00000261160.3

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91671 AN: 151772 Hom.: 27867 Cov.: 31

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.604 AC: 91692 AN: 151886 Hom.: 27868 Cov.: 31 AF XY: 0.605 AC XY: 44899 AN XY: 74228

African (AFR) AF: 0.592 AC: 24500 AN: 41414

American (AMR) AF: 0.628 AC: 9579 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2100 AN: 3468

East Asian (EAS) AF: 0.444 AC: 2278 AN: 5134

South Asian (SAS) AF: 0.511 AC: 2454 AN: 4802

European-Finnish (FIN) AF: 0.704 AC: 7426 AN: 10554

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41449 AN: 67946

Other (OTH) AF: 0.582 AC: 1227 AN: 2108

Alfa AF: 0.587 Hom.: 12330

Bravo AF: 0.597

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.71
PhyloP100		-0.23
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: rs278917; hg19: chr12-41380488;