3-2735938-A-G

Position:

• chr3-2735938-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.56-277A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 559,134 control chromosomes in the GnomAD database, including 217,878 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (51747 hom., cov: 29)
  • Exomes 𝑓: 0.90 (166131 hom.)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.509

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 3-2735938-A-G is Benign according to our data. Variant chr3-2735938-A-G is described in ClinVar as [Benign]. Clinvar id is 1272604.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN4	NM_175607.3	c.56-277A>G		intron_variant		ENST00000418658.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN4	ENST00000418658.6	c.56-277A>G		intron_variant		5	NM_175607.3	P1

Frequencies

GnomAD3 genomes AF: 0.805 AC: 121990 AN: 151626 Hom.: 51733 Cov.: 29

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.938

Gnomad AMR AF: 0.895

Gnomad ASJ AF: 0.885

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.871

Gnomad MID AF: 0.790

Gnomad NFE AF: 0.939

Gnomad OTH AF: 0.831

GnomAD3 exomes AF: 0.885 AC: 190962 AN: 215884 Hom.: 85745 AF XY: 0.887 AC XY: 105532 AN XY: 118942

Gnomad AFR exome AF: 0.495

Gnomad AMR exome AF: 0.937

Gnomad ASJ exome AF: 0.881

Gnomad EAS exome AF: 0.854

Gnomad SAS exome AF: 0.831

Gnomad FIN exome AF: 0.876

Gnomad NFE exome AF: 0.939

Gnomad OTH exome AF: 0.902

GnomAD4 exome AF: 0.899 AC: 366167 AN: 407390 Hom.: 166131 Cov.: 2 AF XY: 0.897 AC XY: 206016 AN XY: 229754

Gnomad4 AFR exome AF: 0.499

Gnomad4 AMR exome AF: 0.935

Gnomad4 ASJ exome AF: 0.885

Gnomad4 EAS exome AF: 0.871

Gnomad4 SAS exome AF: 0.839

Gnomad4 FIN exome AF: 0.882

Gnomad4 NFE exome AF: 0.940

Gnomad4 OTH exome AF: 0.885

GnomAD4 genome AF: 0.804 AC: 122040 AN: 151744 Hom.: 51747 Cov.: 29 AF XY: 0.804 AC XY: 59559 AN XY: 74112

Gnomad4 AFR AF: 0.508

Gnomad4 AMR AF: 0.895

Gnomad4 ASJ AF: 0.885

Gnomad4 EAS AF: 0.871

Gnomad4 SAS AF: 0.835

Gnomad4 FIN AF: 0.871

Gnomad4 NFE AF: 0.939

Gnomad4 OTH AF: 0.833

Alfa AF: 0.878 Hom.: 16853

Bravo AF: 0.794

Asia WGS AF: 0.824 AC: 2868 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	-0.96
CADD	Benign	1.3
DANN	Benign	0.29

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: rs1554198; hg19: chr3-2777622;