rs10510227

Positions:

• chr3-2116033-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.-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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN4	NM_175607.3	c.-145+15394A>G		intron_variant		ENST00000418658.6
CNTN4-AS2	NR_046555.1	n.203-5401T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN4	ENST00000418658.6	c.-145+15394A>G		intron_variant		5	NM_175607.3	P1
CNTN4-AS2	ENST00000447256.2	n.203-5401T>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.0415

Gnomad4 AMR AF: 0.0117

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.0385

Gnomad4 NFE AF: 0.00819

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0187 Hom.: 8

Bravo AF: 0.0281

Asia WGS AF: 0.206 AC: 716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.44

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: rs10510227; hg19: chr3-2157717;