3-2733312-C-T

Position:

• chr3-2733312-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175607.3(CNTN4):​c.56-2903C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,980 control chromosomes in the GnomAD database, including 27,473 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (27473 hom., cov: 32)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN4	NM_175607.3	c.56-2903C>T		intron_variant		ENST00000418658.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN4	ENST00000418658.6	c.56-2903C>T		intron_variant		5	NM_175607.3	P1

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84787 AN: 151864 Hom.: 27480 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.580

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.558 AC: 84781 AN: 151980 Hom.: 27473 Cov.: 32 AF XY: 0.553 AC XY: 41112 AN XY: 74284

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.648

Gnomad4 EAS AF: 0.680

Gnomad4 SAS AF: 0.515

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.738

Gnomad4 OTH AF: 0.576

Alfa AF: 0.699 Hom.: 43275

Bravo AF: 0.542

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.1
DANN	Benign	0.76

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: rs7611703; hg19: chr3-2774996;