rs1403635

Variant names:

• chr3-2248114-G-A
• rs1403635
• NM_175607.3:c.-144-91064G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-2248114-G-A
• chr3-2248114-G-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.-144-91064G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 151,806 control chromosomes in the GnomAD database, including 44,546 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 0.76 (44546 hom., cov: 32)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.-144-91064G>A		intron_variant	Intron 2 of 24	ENST00000418658.6	NP_783200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6	c.-144-91064G>A		intron_variant	Intron 2 of 24	5	NM_175607.3	ENSP00000396010.1

Frequencies

GnomAD3 genomes AF: 0.764 AC: 115909 AN: 151688 Hom.: 44511 Cov.: 32

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.764 AC: 115997 AN: 151806 Hom.: 44546 Cov.: 32 AF XY: 0.768 AC XY: 56957 AN XY: 74194

African (AFR) AF: 0.699 AC: 28954 AN: 41422

American (AMR) AF: 0.814 AC: 12362 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2546 AN: 3468

East Asian (EAS) AF: 0.965 AC: 4985 AN: 5168

South Asian (SAS) AF: 0.829 AC: 4003 AN: 4826

European-Finnish (FIN) AF: 0.797 AC: 8427 AN: 10570

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.768 AC: 52134 AN: 67850

Other (OTH) AF: 0.760 AC: 1598 AN: 2102

Alfa AF: 0.766 Hom.: 39834

Bravo AF: 0.763

Asia WGS AF: 0.887 AC: 3085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.39
DANN	Benign	0.49
PhyloP100		-1.2
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: rs1403635; hg19: chr3-2289798;