rs1516391

chr3-2680636-T-Cchr3-2680636-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.85).
• 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/exons	MANE	UniProt
CNTN4	NM_175607.3	c.56-55579T>C		intron_variant		ENST00000418658.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN4	ENST00000418658.6	c.56-55579T>C		intron_variant		5	NM_175607.3	P1

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

Gnomad4 AFR AF: 0.738

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.568

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.441

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

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: rs1516391; hg19: chr3-2722320;