3-2513799-T-G

Variant names:

• chr3-2513799-T-G
• rs1382875
• NM_175607.3:c.-88-57617T>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.-88-57617T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 151,968 control chromosomes in the GnomAD database, including 5,703 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 0.22 (5703 hom., cov: 32)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.-88-57617T>G		intron_variant	Intron 3 of 24	ENST00000418658.6	NP_783200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6	c.-88-57617T>G		intron_variant	Intron 3 of 24	5	NM_175607.3	ENSP00000396010.1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33666 AN: 151850 Hom.: 5669 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0425

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.222 AC: 33760 AN: 151968 Hom.: 5703 Cov.: 32 AF XY: 0.218 AC XY: 16203 AN XY: 74298

African (AFR) AF: 0.478 AC: 19793 AN: 41380

American (AMR) AF: 0.142 AC: 2167 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 350 AN: 3470

East Asian (EAS) AF: 0.0426 AC: 220 AN: 5162

South Asian (SAS) AF: 0.120 AC: 578 AN: 4824

European-Finnish (FIN) AF: 0.142 AC: 1507 AN: 10578

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8626 AN: 67956

Other (OTH) AF: 0.203 AC: 429 AN: 2112

Alfa AF: 0.150 Hom.: 10349

Bravo AF: 0.233

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.60
DANN	Benign	0.47
PhyloP100		-0.39
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: rs1382875; hg19: chr3-2555483;