3-2583254-G-A

Variant names:

• chr3-2583254-G-A
• rs2619566
• NM_175607.3:c.55+11696G>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.55+11696G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 152,108 control chromosomes in the GnomAD database, including 44,018 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 0.74 (44018 hom., cov: 33)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206
• Publications: 16 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.55+11696G>A		intron_variant	Intron 4 of 24	ENST00000418658.6	NP_783200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6	c.55+11696G>A		intron_variant	Intron 4 of 24	5	NM_175607.3	ENSP00000396010.1

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112872 AN: 151990 Hom.: 44017 Cov.: 33

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.963

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.871

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.858

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.885

Gnomad OTH AF: 0.762

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

GnomAD4 genome AF: 0.742 AC: 112902 AN: 152108 Hom.: 44018 Cov.: 33 AF XY: 0.737 AC XY: 54839 AN XY: 74368

African (AFR) AF: 0.510 AC: 21123 AN: 41450

American (AMR) AF: 0.713 AC: 10895 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.871 AC: 3021 AN: 3468

East Asian (EAS) AF: 0.554 AC: 2856 AN: 5152

South Asian (SAS) AF: 0.618 AC: 2986 AN: 4830

European-Finnish (FIN) AF: 0.858 AC: 9103 AN: 10604

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.885 AC: 60189 AN: 68006

Other (OTH) AF: 0.757 AC: 1599 AN: 2112

Alfa AF: 0.827 Hom.: 166393

Bravo AF: 0.723

Asia WGS AF: 0.522 AC: 1818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.8
DANN	Benign	0.52
PhyloP100		0.21
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: rs2619566; hg19: chr3-2624938;