rs1178517

chr3-2214602-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175607.3(CNTN4):c.-145+113963C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 151,900 control chromosomes in the GnomAD database, including 33,757 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 0.66 (33757 hom., cov: 31)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN4	NM_175607.3	c.-145+113963C>T		intron_variant		ENST00000418658.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN4	ENST00000418658.6	c.-145+113963C>T		intron_variant		5	NM_175607.3	P1
CNTN4	ENST00000422330.5	c.-145+115624C>T		intron_variant		4
CNTN4	ENST00000455083.5	c.-229-47744C>T		intron_variant		4
CNTN4	ENST00000427741.5	c.-145+114953C>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100448 AN: 151784 Hom.: 33742 Cov.: 31

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.662 AC: 100486 AN: 151900 Hom.: 33757 Cov.: 31 AF XY: 0.657 AC XY: 48802 AN XY: 74254

Gnomad4 AFR AF: 0.685

Gnomad4 AMR AF: 0.503

Gnomad4 ASJ AF: 0.623

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.709

Gnomad4 NFE AF: 0.699

Gnomad4 OTH AF: 0.642

Alfa AF: 0.676 Hom.: 45201

Bravo AF: 0.641

Asia WGS AF: 0.538 AC: 1873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.68
Dann	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs1178517; hg19: chr3-2256286;