3-2542692-G-T

Variant names:

• chr3-2542692-G-T
• rs7649181
• NM_175607.3:c.-88-28724G>T

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.-88-28724G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0407 in 152,210 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.041 (185 hom., cov: 32)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0690
• Publications: 1 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=-0.66).
• BP6: Variant 3-2542692-G-T is Benign according to our data. Variant chr3-2542692-G-T is described in ClinVar as [Benign]. Clinvar id is 1241762.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.-88-28724G>T		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.-88-28724G>T		intron_variant	Intron 3 of 24	5	NM_175607.3	ENSP00000396010.1

Frequencies

GnomAD3 genomes AF: 0.0407 AC: 6195 AN: 152092 Hom.: 185 Cov.: 32

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.0758

Gnomad AMR AF: 0.0248

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00703

Gnomad FIN AF: 0.0864

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0612

Gnomad OTH AF: 0.0316

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

GnomAD4 genome AF: 0.0407 AC: 6192 AN: 152210 Hom.: 185 Cov.: 32 AF XY: 0.0406 AC XY: 3019 AN XY: 74416

African (AFR) AF: 0.0107 AC: 445 AN: 41552

American (AMR) AF: 0.0246 AC: 376 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0346 AC: 120 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5150

South Asian (SAS) AF: 0.00704 AC: 34 AN: 4830

European-Finnish (FIN) AF: 0.0864 AC: 917 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0612 AC: 4163 AN: 68006

Other (OTH) AF: 0.0313 AC: 66 AN: 2112

Alfa AF: 0.0492 Hom.: 391

Bravo AF: 0.0348

Asia WGS AF: 0.00491 AC: 17 AN: 3476

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	-0.66
CADD	Benign	15
DANN	Benign	0.71
PhyloP100		0.069
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: rs7649181; hg19: chr3-2584376;