chr3-2692523-A-C

Variant names:

• chr3-2692523-A-C
• rs1024147
• NM_175607.3:c.56-43692A>C

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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 rank	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.56-43692A>C		intron_variant	Intron 4 of 24	ENST00000418658.6	NP_783200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6	c.56-43692A>C		intron_variant	Intron 4 of 24	5	NM_175607.3	ENSP00000396010.1

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

African (AFR) AF: 0.411 AC: 17040 AN: 41440

American (AMR) AF: 0.448 AC: 6830 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1895 AN: 3468

East Asian (EAS) AF: 0.497 AC: 2562 AN: 5158

South Asian (SAS) AF: 0.286 AC: 1379 AN: 4824

European-Finnish (FIN) AF: 0.472 AC: 4976 AN: 10536

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35424 AN: 67946

Other (OTH) AF: 0.494 AC: 1043 AN: 2110

Alfa AF: 0.499 Hom.: 23874

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

May 10, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.4
DANN	Benign	0.45
PhyloP100		1.6
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: rs1024147; hg19: chr3-2734207;