3-2571317-A-G

Position:

• chr3-2571317-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_175607.3(CNTN4):​c.-88-99A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 625,356 control chromosomes in the GnomAD database, including 106,815 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (24035 hom., cov: 33)
  • Exomes 𝑓: 0.58 (82780 hom.)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.111

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 3-2571317-A-G is Benign according to our data. Variant chr3-2571317-A-G is described in ClinVar as [Benign]. Clinvar id is 1286817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.-88-99A>G		intron_variant		ENST00000418658.6	NP_783200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6	c.-88-99A>G		intron_variant		5	NM_175607.3	ENSP00000396010.1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84338 AN: 151922 Hom.: 24028 Cov.: 33

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.565

GnomAD4 exome AF: 0.581 AC: 275077 AN: 473316 Hom.: 82780 Cov.: 4 AF XY: 0.585 AC XY: 146934 AN XY: 251246

Gnomad4 AFR exome AF: 0.487

Gnomad4 AMR exome AF: 0.739

Gnomad4 ASJ exome AF: 0.549

Gnomad4 EAS exome AF: 0.873

Gnomad4 SAS exome AF: 0.669

Gnomad4 FIN exome AF: 0.549

Gnomad4 NFE exome AF: 0.533

Gnomad4 OTH exome AF: 0.574

GnomAD4 genome AF: 0.555 AC: 84378 AN: 152040 Hom.: 24035 Cov.: 33 AF XY: 0.562 AC XY: 41747 AN XY: 74322

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.679

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.879

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.568

Alfa AF: 0.548 Hom.: 31291

Bravo AF: 0.563

Asia WGS AF: 0.771 AC: 2681 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.5
DANN	Benign	0.85

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: rs2616585; hg19: chr3-2613001;