3-2736482-G-A

Position:

• chr3-2736482-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_175607.3(CNTN4):​c.182+141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 358,676 control chromosomes in the GnomAD database, including 141,811 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.80 (51268 hom., cov: 30)
  • Exomes 𝑓: 0.93 (90543 hom.)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.306

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 3-2736482-G-A is Benign according to our data. Variant chr3-2736482-G-A is described in ClinVar as [Benign]. Clinvar id is 1270535.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.182+141G>A		intron_variant		ENST00000418658.6	NP_783200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6	c.182+141G>A		intron_variant		5	NM_175607.3	ENSP00000396010.1

Frequencies

GnomAD3 genomes AF: 0.805 AC: 120972 AN: 150290 Hom.: 51254 Cov.: 30

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.937

Gnomad AMR AF: 0.894

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.803

Gnomad NFE AF: 0.939

Gnomad OTH AF: 0.830

GnomAD4 exome AF: 0.929 AC: 193451 AN: 208268 Hom.: 90543 AF XY: 0.929 AC XY: 101411 AN XY: 109200

Gnomad4 AFR exome AF: 0.446

Gnomad4 AMR exome AF: 0.921

Gnomad4 ASJ exome AF: 0.891

Gnomad4 EAS exome AF: 0.888

Gnomad4 SAS exome AF: 0.822

Gnomad4 FIN exome AF: 0.862

Gnomad4 NFE exome AF: 0.946

Gnomad4 OTH exome AF: 0.889

GnomAD4 genome AF: 0.805 AC: 121022 AN: 150408 Hom.: 51268 Cov.: 30 AF XY: 0.804 AC XY: 59078 AN XY: 73494

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.894

Gnomad4 ASJ AF: 0.886

Gnomad4 EAS AF: 0.871

Gnomad4 SAS AF: 0.832

Gnomad4 FIN AF: 0.870

Gnomad4 NFE AF: 0.939

Gnomad4 OTH AF: 0.832

Alfa AF: 0.862 Hom.: 6852

Bravo AF: 0.794

Asia WGS AF: 0.818 AC: 2836 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1914015; hg19: chr3-2778166;