chr3-2633505-C-T

Variant names:

• chr3-2633505-C-T
• rs9849237
• NM_175607.3:c.55+61947C>T

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+61947C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,120 control chromosomes in the GnomAD database, including 5,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (★).

• Frequency: Genomes: 𝑓 0.25 (5573 hom., cov: 33)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: association criteria provided, single submitter O:1
• Conservation: PhyloP100: -0.771
• Publications: 3 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):

• autism spectrum disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: Illumina
• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

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 (AFR) allele frequency at 95% confidence interval = 0.406 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN4	NM_175607.3	MANE Select	c.55+61947C>T		intron	N/A	NP_783200.1	Q8IWV2-1
	CNTN4	NM_001206955.2		c.55+61947C>T		intron	N/A	NP_001193884.1	Q8IWV2-1
	CNTN4	NM_001350095.2		c.55+61947C>T		intron	N/A	NP_001337024.1	Q8IWV2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN4	ENST00000418658.6	TSL:5 MANE Select	c.55+61947C>T		intron	N/A	ENSP00000396010.1	Q8IWV2-1
	CNTN4	ENST00000397461.5	TSL:5	c.55+61947C>T		intron	N/A	ENSP00000380602.1	Q8IWV2-1
	CNTN4	ENST00000427331.5	TSL:5	c.55+61947C>T		intron	N/A	ENSP00000413642.1	Q8IWV2-1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37630 AN: 152000 Hom.: 5556 Cov.: 33

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0892

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.248 AC: 37704 AN: 152120 Hom.: 5573 Cov.: 33 AF XY: 0.249 AC XY: 18530 AN XY: 74372

African (AFR) AF: 0.411 AC: 17039 AN: 41474

American (AMR) AF: 0.284 AC: 4340 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 475 AN: 3468

East Asian (EAS) AF: 0.0889 AC: 461 AN: 5188

South Asian (SAS) AF: 0.234 AC: 1125 AN: 4814

European-Finnish (FIN) AF: 0.190 AC: 2006 AN: 10574

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11638 AN: 67994

Other (OTH) AF: 0.222 AC: 469 AN: 2114

Alfa AF: 0.192 Hom.: 14132

Bravo AF: 0.258

Asia WGS AF: 0.202 AC: 703 AN: 3478

ClinVar

ClinVar submissions

Significance: association

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	-	Lip and oral cavity carcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.21
DANN	Benign	0.66
PhyloP100		-0.77
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: rs9849237; hg19: chr3-2675189;