3-2493088-G-A

Position:

• chr3-2493088-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.-88-78328G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 152,040 control chromosomes in the GnomAD database, including 34,048 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.67 (34048 hom., cov: 32)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.283

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=-0.73).
• BP6: Variant 3-2493088-G-A is Benign according to our data. Variant chr3-2493088-G-A is described in ClinVar as [Benign]. Clinvar id is 1278611.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.-88-78328G>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.-88-78328G>A		intron_variant		5	NM_175607.3	ENSP00000396010.1

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101316 AN: 151922 Hom.: 34001 Cov.: 32

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.705

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

GnomAD4 genome AF: 0.667 AC: 101417 AN: 152040 Hom.: 34048 Cov.: 32 AF XY: 0.661 AC XY: 49125 AN XY: 74312

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.710

Gnomad4 ASJ AF: 0.754

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.658

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.699

Alfa AF: 0.646 Hom.: 4716

Bravo AF: 0.674

Asia WGS AF: 0.487 AC: 1689 AN: 3470

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.023
DANN	Benign	0.77

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: rs1551997; hg19: chr3-2534772;