chr3-3013563-C-T

Variant names:

• chr3-3013563-C-T
• rs17024684
• NM_175607.3:c.1487-12539C>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.1487-12539C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0771 in 152,000 control chromosomes in the GnomAD database, including 547 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 0.077 (547 hom., cov: 32)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 7 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):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• autism spectrum disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: Illumina

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.127 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN4	NM_175607.3	MANE Select	c.1487-12539C>T		intron	N/A	NP_783200.1
	CNTN4	NM_001206955.2		c.1487-12539C>T		intron	N/A	NP_001193884.1
	CNTN4	NM_001350095.2		c.1487-12539C>T		intron	N/A	NP_001337024.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN4	ENST00000418658.6	TSL:5 MANE Select	c.1487-12539C>T		intron	N/A	ENSP00000396010.1
	CNTN4	ENST00000397459.6	TSL:1	c.503-12539C>T		intron	N/A	ENSP00000380600.2
	CNTN4	ENST00000397461.5	TSL:5	c.1487-12539C>T		intron	N/A	ENSP00000380602.1

Frequencies

GnomAD3 genomes AF: 0.0773 AC: 11733 AN: 151882 Hom.: 548 Cov.: 32

Gnomad AFR AF: 0.0392

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.0665

Gnomad FIN AF: 0.0703

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0877

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.0771 AC: 11717 AN: 152000 Hom.: 547 Cov.: 32 AF XY: 0.0785 AC XY: 5828 AN XY: 74264

African (AFR) AF: 0.0391 AC: 1621 AN: 41502

American (AMR) AF: 0.110 AC: 1681 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 373 AN: 3466

East Asian (EAS) AF: 0.136 AC: 698 AN: 5146

South Asian (SAS) AF: 0.0657 AC: 316 AN: 4810

European-Finnish (FIN) AF: 0.0703 AC: 739 AN: 10508

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.0877 AC: 5963 AN: 67974

Other (OTH) AF: 0.102 AC: 215 AN: 2116

Alfa AF: 0.0822 Hom.: 1279

Bravo AF: 0.0804

Asia WGS AF: 0.0880 AC: 306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.3
DANN	Benign	0.76
PhyloP100		-0.0050
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: rs17024684; hg19: chr3-3055247;