3-3040319-T-A

Position:

• chr3-3040319-T-A

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+48T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,391,810 control chromosomes in the GnomAD database, including 13,723 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2890 hom., cov: 34)
  • Exomes 𝑓: 0.13 (10833 hom.)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.451

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=-0.79).
• BP6: Variant 3-3040319-T-A is Benign according to our data. Variant chr3-3040319-T-A is described in ClinVar as [Benign]. Clinvar id is 1262848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.2398+48T>A		intron_variant		ENST00000418658.6	NP_783200.1
CNTN4-AS1	NR_046554.1	n.354A>T		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+48T>A		intron_variant		5	NM_175607.3	ENSP00000396010	P1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26774 AN: 152118 Hom.: 2882 Cov.: 34

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0906

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.169

GnomAD3 exomes AF: 0.135 AC: 32728 AN: 242260 Hom.: 2554 AF XY: 0.132 AC XY: 17240 AN XY: 131102

Gnomad AFR exome AF: 0.317

Gnomad AMR exome AF: 0.0912

Gnomad ASJ exome AF: 0.200

Gnomad EAS exome AF: 0.184

Gnomad SAS exome AF: 0.103

Gnomad FIN exome AF: 0.0930

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.125 AC: 155128 AN: 1239574 Hom.: 10833 Cov.: 17 AF XY: 0.125 AC XY: 78225 AN XY: 627476

Gnomad4 AFR exome AF: 0.307

Gnomad4 AMR exome AF: 0.0936

Gnomad4 ASJ exome AF: 0.201

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.0893

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.176 AC: 26814 AN: 152236 Hom.: 2890 Cov.: 34 AF XY: 0.173 AC XY: 12906 AN XY: 74416

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.0906

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.167

Alfa AF: 0.157 Hom.: 373

Bravo AF: 0.187

Asia WGS AF: 0.120 AC: 419 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	-0.79
CADD	Benign	2.2
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs339283; hg19: chr3-3082003;