3-2290455-T-C

Position:

• chr3-2290455-T-C

Variant summary

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

The NM_175607.3(CNTN4):​c.-144-48723T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 152,256 control chromosomes in the GnomAD database, including 61,609 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 0.90 (61609 hom., cov: 33)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.-144-48723T>C		intron_variant		ENST00000418658.6	NP_783200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6	c.-144-48723T>C		intron_variant		5	NM_175607.3	ENSP00000396010	P1

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136753 AN: 152138 Hom.: 61538 Cov.: 33

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.922

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.960

Gnomad SAS AF: 0.927

Gnomad FIN AF: 0.864

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.870

Gnomad OTH AF: 0.886

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

GnomAD4 genome AF: 0.899 AC: 136884 AN: 152256 Hom.: 61609 Cov.: 33 AF XY: 0.900 AC XY: 66976 AN XY: 74432

Gnomad4 AFR AF: 0.937

Gnomad4 AMR AF: 0.922

Gnomad4 ASJ AF: 0.892

Gnomad4 EAS AF: 0.960

Gnomad4 SAS AF: 0.927

Gnomad4 FIN AF: 0.864

Gnomad4 NFE AF: 0.870

Gnomad4 OTH AF: 0.888

Alfa AF: 0.876 Hom.: 71539

Bravo AF: 0.904

Asia WGS AF: 0.935 AC: 3251 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.39

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: rs1720199; hg19: chr3-2332139;