rs312273

Variant names:

• chr12-40853940-G-A
• rs312273
• NM_001843.4:c.-76-54417G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-40853940-G-A
• chr12-40853940-G-C
• chr12-40853940-G-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.-76-54417G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 150,186 control chromosomes in the GnomAD database, including 25,152 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 (25152 hom., cov: 27)
• Consequence: CNTN1 NM_001843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.482
• Publications: 6 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN1	NM_001843.4	c.-76-54417G>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.-76-54417G>A		intron_variant	Intron 1 of 23	1	NM_001843.4	ENSP00000447006.1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 84023 AN: 150068 Hom.: 25115 Cov.: 27

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.560 AC: 84100 AN: 150186 Hom.: 25152 Cov.: 27 AF XY: 0.559 AC XY: 40957 AN XY: 73214

African (AFR) AF: 0.800 AC: 32754 AN: 40958

American (AMR) AF: 0.528 AC: 7876 AN: 14922

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1776 AN: 3456

East Asian (EAS) AF: 0.383 AC: 1946 AN: 5078

South Asian (SAS) AF: 0.444 AC: 2078 AN: 4680

European-Finnish (FIN) AF: 0.502 AC: 5189 AN: 10330

Middle Eastern (MID) AF: 0.497 AC: 143 AN: 288

European-Non Finnish (NFE) AF: 0.457 AC: 30850 AN: 67502

Other (OTH) AF: 0.527 AC: 1088 AN: 2066

Alfa AF: 0.512 Hom.: 6999

Bravo AF: 0.569

Asia WGS AF: 0.429 AC: 1495 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.7
DANN	Benign	0.29
PhyloP100		0.48
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: rs312273; hg19: chr12-41247742;