3-3039832-A-G

Position:

• chr3-3039832-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.2164-205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 573,194 control chromosomes in the GnomAD database, including 10,286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (5258 hom., cov: 33)
  • Exomes 𝑓: 0.14 (5028 hom.)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.47

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-AS1 (HGNC:39985): (CNTN4 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-3039832-A-G is Benign according to our data. Variant chr3-3039832-A-G is described in ClinVar as [Benign]. Clinvar id is 1288342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.2164-205A>G		intron_variant		ENST00000418658.6	NP_783200.1
CNTN4-AS1	NR_046554.1	n.841T>C		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6	c.2164-205A>G		intron_variant		5	NM_175607.3	ENSP00000396010	P1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33359 AN: 151926 Hom.: 5247 Cov.: 33

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0921

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.206

GnomAD4 exome AF: 0.138 AC: 58261 AN: 421150 Hom.: 5028 Cov.: 3 AF XY: 0.136 AC XY: 30545 AN XY: 224822

Gnomad4 AFR exome AF: 0.448

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.216

Gnomad4 EAS exome AF: 0.176

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.0874

Gnomad4 NFE exome AF: 0.127

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.220 AC: 33407 AN: 152044 Hom.: 5258 Cov.: 33 AF XY: 0.214 AC XY: 15937 AN XY: 74344

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.0921

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.204

Alfa AF: 0.149 Hom.: 3437

Bravo AF: 0.236

Asia WGS AF: 0.142 AC: 495 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	-0.83
CADD	Benign	0.030
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs339287; hg19: chr3-3081516;