3-2492876-C-A

Variant names:

• chr3-2492876-C-A
• rs1125102
• NM_175607.3:c.-88-78540C>A

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.-88-78540C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 151,884 control chromosomes in the GnomAD database, including 9,818 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.35 (9818 hom., cov: 32)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.275
• Publications: 3 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=-0.76).
• BP6: Variant 3-2492876-C-A is Benign according to our data. Variant chr3-2492876-C-A is described in ClinVar as [Benign]. Clinvar id is 1289354.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.-88-78540C>A		intron_variant	Intron 3 of 24	ENST00000418658.6	NP_783200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6	c.-88-78540C>A		intron_variant	Intron 3 of 24	5	NM_175607.3	ENSP00000396010.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52691 AN: 151766 Hom.: 9818 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.347 AC: 52711 AN: 151884 Hom.: 9818 Cov.: 32 AF XY: 0.346 AC XY: 25691 AN XY: 74200

African (AFR) AF: 0.209 AC: 8660 AN: 41414

American (AMR) AF: 0.463 AC: 7057 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1834 AN: 3470

East Asian (EAS) AF: 0.397 AC: 2052 AN: 5170

South Asian (SAS) AF: 0.312 AC: 1502 AN: 4812

European-Finnish (FIN) AF: 0.350 AC: 3691 AN: 10538

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26606 AN: 67926

Other (OTH) AF: 0.376 AC: 792 AN: 2106

Alfa AF: 0.379 Hom.: 46556

Bravo AF: 0.352

Asia WGS AF: 0.338 AC: 1176 AN: 3472

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	-0.76
CADD	Benign	11
DANN	Benign	0.77
PhyloP100		0.28
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: rs1125102; hg19: chr3-2534560;