rs4684343

Variant names:

• chr3-2349414-G-A
• rs4684343
• NM_175607.3:c.-89+10181G>A

Variant summary

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

The NM_175607.3(CNTN4):​c.-89+10181G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 151,864 control chromosomes in the GnomAD database, including 13,926 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 0.42 (13926 hom., cov: 32)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.-89+10181G>A		intron_variant	Intron 3 of 24	ENST00000418658.6	NP_783200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6	c.-89+10181G>A		intron_variant	Intron 3 of 24	5	NM_175607.3	ENSP00000396010.1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63212 AN: 151746 Hom.: 13927 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.416 AC: 63227 AN: 151864 Hom.: 13926 Cov.: 32 AF XY: 0.422 AC XY: 31334 AN XY: 74190

African (AFR) AF: 0.301 AC: 12454 AN: 41410

American (AMR) AF: 0.407 AC: 6216 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1396 AN: 3470

East Asian (EAS) AF: 0.798 AC: 4107 AN: 5148

South Asian (SAS) AF: 0.499 AC: 2402 AN: 4814

European-Finnish (FIN) AF: 0.481 AC: 5067 AN: 10526

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 30045 AN: 67922

Other (OTH) AF: 0.446 AC: 942 AN: 2110

Alfa AF: 0.438 Hom.: 7753

Bravo AF: 0.404

Asia WGS AF: 0.603 AC: 2090 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.77
PhyloP100		-0.67
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: rs4684343; hg19: chr3-2391098;