3-3040341-G-T

Position:

• chr3-3040341-G-T

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.2398+70G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,159,798 control chromosomes in the GnomAD database, including 35,995 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5238 hom., cov: 34)
  • Exomes 𝑓: 0.24 (30757 hom.)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.09

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=-0.88).
• BP6: Variant 3-3040341-G-T is Benign according to our data. Variant chr3-3040341-G-T is described in ClinVar as [Benign]. Clinvar id is 1288739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.2398+70G>T		intron_variant		ENST00000418658.6	NP_783200.1
CNTN4-AS1	NR_046554.1	n.332C>A		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6	c.2398+70G>T		intron_variant		5	NM_175607.3	ENSP00000396010	P1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38928 AN: 152046 Hom.: 5222 Cov.: 34

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.243 AC: 244939 AN: 1007634 Hom.: 30757 Cov.: 13 AF XY: 0.242 AC XY: 125421 AN XY: 518490

Gnomad4 AFR exome AF: 0.301

Gnomad4 AMR exome AF: 0.197

Gnomad4 ASJ exome AF: 0.302

Gnomad4 EAS exome AF: 0.141

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.212

Gnomad4 NFE exome AF: 0.253

Gnomad4 OTH exome AF: 0.254

GnomAD4 genome AF: 0.256 AC: 38973 AN: 152164 Hom.: 5238 Cov.: 34 AF XY: 0.252 AC XY: 18742 AN XY: 74386

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.275

Alfa AF: 0.168 Hom.: 381

Bravo AF: 0.262

Asia WGS AF: 0.162 AC: 562 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	-0.88
CADD	Benign	0.76
DANN	Benign	0.53

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: rs4685596; hg19: chr3-3082025;