3-2633505-C-T

Position:

• chr3-2633505-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.55+61947C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,120 control chromosomes in the GnomAD database, including 5,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (★).

• Frequency: Genomes: 𝑓 0.25 (5573 hom., cov: 33)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: association criteria provided, single submitter O:1
• Conservation: PhyloP100: -0.771

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.55+61947C>T		intron_variant		ENST00000418658.6	NP_783200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6	c.55+61947C>T		intron_variant		5	NM_175607.3	ENSP00000396010.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37630 AN: 152000 Hom.: 5556 Cov.: 33

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0892

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.248 AC: 37704 AN: 152120 Hom.: 5573 Cov.: 33 AF XY: 0.249 AC XY: 18530 AN XY: 74372

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.0889

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.222

Alfa AF: 0.178 Hom.: 5433

Bravo AF: 0.258

Asia WGS AF: 0.202 AC: 703 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Lip and oral cavity carcinoma Other:1

association, criteria provided, single submitter

case-control

Department of Biological Science, Sunandan Divatia School of Science, NMIMS University

Jan 01, 2016

The homozygous WT (CC) genotype showed a higher frequency in cases as compared to controls and a significant association was observed with an OR of 1.41 (1.09-1.82). The heterozygous genotype indicated decreased risk to oral cancer with an OR 0.75 (0.58-0.97) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.21
DANN	Benign	0.66

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: rs9849237; hg19: chr3-2675189;