3-2238551-A-G

Variant names:

• chr3-2238551-A-G
• rs9873966
• NM_175607.3:c.-144-100627A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.91).
• 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 rank	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.-144-100627A>G		intron_variant	Intron 2 of 24	ENST00000418658.6	NP_783200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6	c.-144-100627A>G		intron_variant	Intron 2 of 24	5	NM_175607.3	ENSP00000396010.1
CNTN4	ENST00000422330.5	c.-144-100627A>G		intron_variant	Intron 1 of 4	4		ENSP00000408594.1
CNTN4	ENST00000455083.5	c.-229-23795A>G		intron_variant	Intron 2 of 5	4		ENSP00000390560.1
CNTN4	ENST00000427741.5	n.-144-100627A>G		intron_variant	Intron 2 of 20	2		ENSP00000396719.1

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

African (AFR) AF: 0.205 AC: 8470 AN: 41400

American (AMR) AF: 0.338 AC: 5106 AN: 15112

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 730 AN: 3464

East Asian (EAS) AF: 0.313 AC: 1593 AN: 5094

South Asian (SAS) AF: 0.381 AC: 1808 AN: 4748

European-Finnish (FIN) AF: 0.226 AC: 2345 AN: 10384

Middle Eastern (MID) AF: 0.289 AC: 82 AN: 284

European-Non Finnish (NFE) AF: 0.196 AC: 13305 AN: 67818

Other (OTH) AF: 0.232 AC: 486 AN: 2092

Alfa AF: 0.217 Hom.: 1862

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
PhyloP100		-0.38
PromoterAI		0.0012	Neutral
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: rs9873966; hg19: chr3-2280235;