chr3-2378926-A-G

Variant names:

• chr3-2378926-A-G
• rs17013494
• NM_175607.3:c.-89+39693A>G

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+39693A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0716 in 152,186 control chromosomes in the GnomAD database, including 930 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 0.072 (930 hom., cov: 32)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.753
• Publications: 0 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175607.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN4	NM_175607.3	MANE Select	c.-89+39693A>G		intron	N/A	NP_783200.1
	CNTN4	NM_001206955.2		c.-89+39693A>G		intron	N/A	NP_001193884.1
	CNTN4	NM_001350095.2		c.-89+39693A>G		intron	N/A	NP_001337024.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN4	ENST00000418658.6	TSL:5 MANE Select	c.-89+39693A>G		intron	N/A	ENSP00000396010.1
	CNTN4	ENST00000397461.5	TSL:5	c.-89+39693A>G		intron	N/A	ENSP00000380602.1
	CNTN4	ENST00000422330.5	TSL:4	c.-89+39693A>G		intron	N/A	ENSP00000408594.1

Frequencies

GnomAD3 genomes AF: 0.0716 AC: 10893 AN: 152068 Hom.: 932 Cov.: 32

Gnomad AFR AF: 0.0166

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0892

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.0918

Gnomad FIN AF: 0.0709

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0696

Gnomad OTH AF: 0.0674

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

GnomAD4 genome AF: 0.0716 AC: 10898 AN: 152186 Hom.: 930 Cov.: 32 AF XY: 0.0752 AC XY: 5596 AN XY: 74410

African (AFR) AF: 0.0166 AC: 688 AN: 41540

American (AMR) AF: 0.0890 AC: 1361 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0510 AC: 177 AN: 3470

East Asian (EAS) AF: 0.498 AC: 2558 AN: 5132

South Asian (SAS) AF: 0.0919 AC: 443 AN: 4820

European-Finnish (FIN) AF: 0.0709 AC: 752 AN: 10606

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0696 AC: 4731 AN: 68014

Other (OTH) AF: 0.0700 AC: 148 AN: 2114

Alfa AF: 0.0645 Hom.: 60

Bravo AF: 0.0727

Asia WGS AF: 0.250 AC: 866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.72
PhyloP100		-0.75
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: rs17013494; hg19: chr3-2420610;