rs9873966

Positions:

• chr3-2238551-A-G

Variant summary

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

The NM_175607.3(CNTN4):​c.-144-100627A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 151,308 control chromosomes in the GnomAD database, including 4,106 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 0.23 (4106 hom., cov: 29)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN4	NM_175607.3	c.-144-100627A>G		intron_variant		ENST00000418658.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN4	ENST00000418658.6	c.-144-100627A>G		intron_variant		5	NM_175607.3	P1
CNTN4	ENST00000422330.5	c.-144-100627A>G		intron_variant		4
CNTN4	ENST00000455083.5	c.-229-23795A>G		intron_variant		4
CNTN4	ENST00000427741.5	c.-144-100627A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34048 AN: 151188 Hom.: 4095 Cov.: 29

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.225 AC: 34096 AN: 151308 Hom.: 4106 Cov.: 29 AF XY: 0.232 AC XY: 17132 AN XY: 73908

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.232

Alfa AF: 0.218 Hom.: 1677

Bravo AF: 0.234

Asia WGS AF: 0.336 AC: 1167 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.50

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: rs9873966; hg19: chr3-2280235;