chr3-2680636-T-C

Variant names:

• chr3-2680636-T-C
• rs1516391
• NM_175607.3:c.56-55579T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175607.3(CNTN4):​c.56-55579T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 152,052 control chromosomes in the GnomAD database, including 19,388 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 0.47 (19388 hom., cov: 33)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• autism spectrum disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.56-55579T>C		intron_variant	Intron 4 of 24	ENST00000418658.6	NP_783200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6	c.56-55579T>C		intron_variant	Intron 4 of 24	5	NM_175607.3	ENSP00000396010.1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 72064 AN: 151934 Hom.: 19332 Cov.: 33

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.475 AC: 72188 AN: 152052 Hom.: 19388 Cov.: 33 AF XY: 0.475 AC XY: 35315 AN XY: 74316

African (AFR) AF: 0.738 AC: 30592 AN: 41480

American (AMR) AF: 0.486 AC: 7416 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1173 AN: 3468

East Asian (EAS) AF: 0.374 AC: 1935 AN: 5174

South Asian (SAS) AF: 0.568 AC: 2742 AN: 4824

European-Finnish (FIN) AF: 0.328 AC: 3457 AN: 10554

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23589 AN: 67976

Other (OTH) AF: 0.441 AC: 930 AN: 2110

Alfa AF: 0.434 Hom.: 2733

Bravo AF: 0.493

Asia WGS AF: 0.494 AC: 1718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.53
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1516391; hg19: chr3-2722320;