NM_175607.3:c.55+9982A>G

Variant names:

• chr3-2581540-A-G
• rs7650485
• NM_175607.3:c.55+9982A>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.55+9982A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.063 in 152,224 control chromosomes in the GnomAD database, including 642 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 0.063 (642 hom., cov: 32)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390
• 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 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.55+9982A>G		intron_variant	Intron 4 of 24	ENST00000418658.6	NP_783200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6	c.55+9982A>G		intron_variant	Intron 4 of 24	5	NM_175607.3	ENSP00000396010.1

Frequencies

GnomAD3 genomes AF: 0.0630 AC: 9580 AN: 152106 Hom.: 644 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.0160

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00645

Gnomad OTH AF: 0.0516

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

GnomAD4 genome AF: 0.0630 AC: 9594 AN: 152224 Hom.: 642 Cov.: 32 AF XY: 0.0659 AC XY: 4905 AN XY: 74420

African (AFR) AF: 0.127 AC: 5277 AN: 41516

American (AMR) AF: 0.104 AC: 1594 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 44 AN: 3470

East Asian (EAS) AF: 0.220 AC: 1133 AN: 5150

South Asian (SAS) AF: 0.168 AC: 812 AN: 4824

European-Finnish (FIN) AF: 0.0160 AC: 170 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00645 AC: 439 AN: 68026

Other (OTH) AF: 0.0572 AC: 121 AN: 2114

Alfa AF: 0.0317 Hom.: 86

Bravo AF: 0.0727

Asia WGS AF: 0.213 AC: 741 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.0
DANN	Benign	0.46
PhyloP100		0.039
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: rs7650485; hg19: chr3-2623224;