rs1178517

Variant names:

• chr3-2214602-C-T
• rs1178517
• NM_175607.3:c.-145+113963C>T

Variant summary

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

The NM_175607.3(CNTN4):​c.-145+113963C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 151,900 control chromosomes in the GnomAD database, including 33,757 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 0.66 (33757 hom., cov: 31)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266
• Publications: 3 publications found

Genes affected

CNTN4 (HGNC:2174): (contactin 4) This gene encodes a member of the contactin family of immunoglobulins. Contactins are axon-associated cell adhesion molecules that function in neuronal network formation and plasticity. The encoded protein is a glycosylphosphatidylinositol-anchored neuronal membrane protein that may play a role in the formation of axon connections in the developing nervous system. Deletion or mutation of this gene may play a role in 3p deletion syndrome and autism spectrum disorders. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2011]

CNTN4 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: Illumina
• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175607.3. 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
	CNTN4	NM_175607.3	MANE Select	c.-145+113963C>T		intron	N/A	NP_783200.1	Q8IWV2-1
	CNTN4	NM_001350095.2		c.-145+114953C>T		intron	N/A	NP_001337024.1	Q8IWV2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN4	ENST00000418658.6	TSL:5 MANE Select	c.-145+113963C>T		intron	N/A	ENSP00000396010.1	Q8IWV2-1
	CNTN4	ENST00000422330.5	TSL:4	c.-145+115624C>T		intron	N/A	ENSP00000408594.1	C9JMQ2
	CNTN4	ENST00000455083.5	TSL:4	c.-229-47744C>T		intron	N/A	ENSP00000390560.1	C9JGK9

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100448 AN: 151784 Hom.: 33742 Cov.: 31

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.662 AC: 100486 AN: 151900 Hom.: 33757 Cov.: 31 AF XY: 0.657 AC XY: 48802 AN XY: 74254

African (AFR) AF: 0.685 AC: 28341 AN: 41396

American (AMR) AF: 0.503 AC: 7673 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2159 AN: 3464

East Asian (EAS) AF: 0.474 AC: 2443 AN: 5154

South Asian (SAS) AF: 0.593 AC: 2859 AN: 4824

European-Finnish (FIN) AF: 0.709 AC: 7476 AN: 10550

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47498 AN: 67940

Other (OTH) AF: 0.642 AC: 1356 AN: 2112

Alfa AF: 0.676 Hom.: 54034

Bravo AF: 0.641

Asia WGS AF: 0.538 AC: 1873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.68
DANN	Benign	0.40
PhyloP100		-0.27
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: rs1178517; hg19: chr3-2256286;