3-2692523-A-C

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.56-43692A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,932 control chromosomes in the GnomAD database, including 17,279 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.47 (17279 hom., cov: 32)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.58

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-2692523-A-C is Benign according to our data. Variant chr3-2692523-A-C is described in ClinVar as [Benign]. Clinvar id is 1258885.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN4	NM_175607.3	c.56-43692A>C		intron_variant		ENST00000418658.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN4	ENST00000418658.6	c.56-43692A>C		intron_variant		5	NM_175607.3	P1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71792 AN: 151814 Hom.: 17286 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.473 AC: 71803 AN: 151932 Hom.: 17279 Cov.: 32 AF XY: 0.466 AC XY: 34608 AN XY: 74246

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.494

Alfa AF: 0.501 Hom.: 18174

Bravo AF: 0.475

Asia WGS AF: 0.373 AC: 1297 AN: 3478

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

May 10, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	7.4
Dann	Benign	0.45

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: rs1024147; hg19: chr3-2734207;