rs7623683

Variant names:

• chr3-2784519-G-C
• rs7623683
• NM_175607.3:c.359-34967G>C

Variant summary

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

The NM_175607.3(CNTN4):​c.359-34967G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 152,252 control chromosomes in the GnomAD database, including 63,417 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 0.91 (63417 hom., cov: 32)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.763
• Publications: 2 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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.359-34967G>C		intron_variant	Intron 6 of 24	ENST00000418658.6	NP_783200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6	c.359-34967G>C		intron_variant	Intron 6 of 24	5	NM_175607.3	ENSP00000396010.1

Frequencies

GnomAD3 genomes AF: 0.911 AC: 138666 AN: 152134 Hom.: 63394 Cov.: 32

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.926

Gnomad ASJ AF: 0.961

Gnomad EAS AF: 0.960

Gnomad SAS AF: 0.976

Gnomad FIN AF: 0.970

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.937

Gnomad OTH AF: 0.918

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

GnomAD4 genome AF: 0.911 AC: 138745 AN: 152252 Hom.: 63417 Cov.: 32 AF XY: 0.915 AC XY: 68096 AN XY: 74446

African (AFR) AF: 0.831 AC: 34512 AN: 41510

American (AMR) AF: 0.926 AC: 14156 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.961 AC: 3335 AN: 3472

East Asian (EAS) AF: 0.960 AC: 4977 AN: 5182

South Asian (SAS) AF: 0.975 AC: 4712 AN: 4832

European-Finnish (FIN) AF: 0.970 AC: 10295 AN: 10614

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.937 AC: 63722 AN: 68034

Other (OTH) AF: 0.915 AC: 1928 AN: 2108

Alfa AF: 0.923 Hom.: 8072

Bravo AF: 0.905

Asia WGS AF: 0.947 AC: 3295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.51
DANN	Benign	0.46
PhyloP100		-0.76
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: rs7623683; hg19: chr3-2826203;