chr3-2116033-A-G

Variant names:

• chr3-2116033-A-G
• rs10510227
• NM_175607.3:c.-145+15394A>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.-145+15394A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.034 in 152,244 control chromosomes in the GnomAD database, including 299 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 0.034 (299 hom., cov: 32)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• Publications: 1 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-AS2 (HGNC:39986): (CNTN4 antisense RNA 2)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175607.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN4	NM_175607.3	MANE Select	c.-145+15394A>G		intron	N/A	NP_783200.1
	CNTN4	NM_001350095.2		c.-145+16384A>G		intron	N/A	NP_001337024.1
	CNTN4-AS2	NR_046555.1		n.203-5401T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN4	ENST00000418658.6	TSL:5 MANE Select	c.-145+15394A>G		intron	N/A	ENSP00000396010.1
	CNTN4	ENST00000422330.5	TSL:4	c.-145+17055A>G		intron	N/A	ENSP00000408594.1
	CNTN4	ENST00000455083.5	TSL:4	c.-230+15394A>G		intron	N/A	ENSP00000390560.1

Frequencies

GnomAD3 genomes AF: 0.0339 AC: 5159 AN: 152126 Hom.: 295 Cov.: 32

Gnomad AFR AF: 0.0414

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.0385

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00819

Gnomad OTH AF: 0.0368

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

GnomAD4 genome AF: 0.0340 AC: 5176 AN: 152244 Hom.: 299 Cov.: 32 AF XY: 0.0389 AC XY: 2894 AN XY: 74428

African (AFR) AF: 0.0415 AC: 1726 AN: 41558

American (AMR) AF: 0.0117 AC: 179 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3472

East Asian (EAS) AF: 0.217 AC: 1113 AN: 5140

South Asian (SAS) AF: 0.221 AC: 1063 AN: 4820

European-Finnish (FIN) AF: 0.0385 AC: 409 AN: 10614

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00819 AC: 557 AN: 68026

Other (OTH) AF: 0.0374 AC: 79 AN: 2114

Alfa AF: 0.0167 Hom.: 189

Bravo AF: 0.0281

Asia WGS AF: 0.206 AC: 716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.44
PhyloP100		-0.032
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: rs10510227; hg19: chr3-2157717;