12-40810126-A-G

Variant names:

• chr12-40810126-A-G
• rs1596516
• NM_001843.4:c.-76-98231A>G

Variant summary

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

The NM_001843.4(CNTN1):​c.-76-98231A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 151,980 control chromosomes in the GnomAD database, including 24,363 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 0.56 (24363 hom., cov: 32)
• Consequence: CNTN1 NM_001843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.749 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.-76-98231A>G		intron	N/A	NP_001834.2
	CNTN1	NM_001256063.2		c.-76-98231A>G		intron	N/A	NP_001242992.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN1	ENST00000551295.7	TSL:1 MANE Select	c.-76-98231A>G		intron	N/A	ENSP00000447006.1
	CNTN1	ENST00000547702.5	TSL:2	c.-76-98231A>G		intron	N/A	ENSP00000448004.1
	CNTN1	ENST00000552248.5	TSL:3	c.-77+67657A>G		intron	N/A	ENSP00000447860.1

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85242 AN: 151862 Hom.: 24325 Cov.: 32

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.561 AC: 85317 AN: 151980 Hom.: 24363 Cov.: 32 AF XY: 0.565 AC XY: 41989 AN XY: 74274

African (AFR) AF: 0.481 AC: 19914 AN: 41436

American (AMR) AF: 0.645 AC: 9838 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1758 AN: 3466

East Asian (EAS) AF: 0.769 AC: 3978 AN: 5172

South Asian (SAS) AF: 0.548 AC: 2643 AN: 4822

European-Finnish (FIN) AF: 0.635 AC: 6695 AN: 10544

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.569 AC: 38676 AN: 67972

Other (OTH) AF: 0.563 AC: 1188 AN: 2112

Alfa AF: 0.551 Hom.: 4926

Bravo AF: 0.566

Asia WGS AF: 0.651 AC: 2259 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.6
DANN	Benign	0.73
PhyloP100		0.20
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: rs1596516; hg19: chr12-41203928;