rs10506176

Variant names:

• chr12-40880998-G-T
• rs10506176
• NM_001843.4:c.-76-27359G>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.-76-27359G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0491 in 152,008 control chromosomes in the GnomAD database, including 410 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 0.049 (410 hom., cov: 32)
• Consequence: CNTN1 NM_001843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640
• Publications: 2 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), Orphanet, Ambry Genetics
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN1	NM_001843.4	MANE Select	c.-76-27359G>T		intron	N/A	NP_001834.2
	CNTN1	NM_001256063.2		c.-76-27359G>T		intron	N/A	NP_001242992.1	Q12860-3
	CNTN1	NM_001256064.2		c.-76-27359G>T		intron	N/A	NP_001242993.1	Q12860-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN1	ENST00000551295.7	TSL:1 MANE Select	c.-76-27359G>T		intron	N/A	ENSP00000447006.1	Q12860-1
	CNTN1	ENST00000547849.6	TSL:1	c.-76-27359G>T		intron	N/A	ENSP00000448653.1	Q12860-3
	CNTN1	ENST00000901030.1		c.-76-27359G>T		intron	N/A	ENSP00000571089.1

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 7445 AN: 151890 Hom.: 409 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.00838

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0141

Gnomad OTH AF: 0.0378

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

GnomAD4 genome AF: 0.0491 AC: 7466 AN: 152008 Hom.: 410 Cov.: 32 AF XY: 0.0473 AC XY: 3518 AN XY: 74342

African (AFR) AF: 0.142 AC: 5880 AN: 41490

American (AMR) AF: 0.0225 AC: 343 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3468

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5174

South Asian (SAS) AF: 0.0126 AC: 61 AN: 4828

European-Finnish (FIN) AF: 0.00838 AC: 89 AN: 10620

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0140 AC: 953 AN: 67854

Other (OTH) AF: 0.0374 AC: 79 AN: 2114

Alfa AF: 0.0218 Hom.: 162

Bravo AF: 0.0539

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.89
DANN	Benign	0.54
PhyloP100		-0.64
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10506176;

hg19: chr12-41274800;

COSMIC: COSV73505155;