rs149467

Variant names:

• chr3-3000135-C-T
• rs149467
• NM_175607.3:c.1486+11663C>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.1486+11663C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 151,744 control chromosomes in the GnomAD database, including 1,934 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 0.16 (1934 hom., cov: 32)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.1486+11663C>T		intron_variant	Intron 14 of 24	ENST00000418658.6	NP_783200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6	c.1486+11663C>T		intron_variant	Intron 14 of 24	5	NM_175607.3	ENSP00000396010.1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23655 AN: 151626 Hom.: 1931 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.0838

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.156 AC: 23660 AN: 151744 Hom.: 1934 Cov.: 32 AF XY: 0.152 AC XY: 11266 AN XY: 74170

African (AFR) AF: 0.155 AC: 6400 AN: 41320

American (AMR) AF: 0.126 AC: 1916 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 585 AN: 3468

East Asian (EAS) AF: 0.271 AC: 1398 AN: 5156

South Asian (SAS) AF: 0.215 AC: 1034 AN: 4806

European-Finnish (FIN) AF: 0.0838 AC: 880 AN: 10502

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10901 AN: 67936

Other (OTH) AF: 0.143 AC: 300 AN: 2104

Alfa AF: 0.160 Hom.: 6737

Bravo AF: 0.159

Asia WGS AF: 0.215 AC: 749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.20
PhyloP100		0.025
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: rs149467; hg19: chr3-3041819;