chr3-2431101-G-A

Variant names:

• chr3-2431101-G-A
• rs2134358
• NM_175607.3:c.-89+91868G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175607.3(CNTN4):​c.-89+91868G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 151,996 control chromosomes in the GnomAD database, including 26,015 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 0.57 (26015 hom., cov: 32)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 6 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.666 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.-89+91868G>A		intron	N/A	NP_783200.1
	CNTN4	NM_001206955.2		c.-89+91868G>A		intron	N/A	NP_001193884.1
	CNTN4	NM_001350095.2		c.-89+91868G>A		intron	N/A	NP_001337024.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN4	ENST00000418658.6	TSL:5 MANE Select	c.-89+91868G>A		intron	N/A	ENSP00000396010.1
	CNTN4	ENST00000397461.5	TSL:5	c.-89+91868G>A		intron	N/A	ENSP00000380602.1
	CNTN4	ENST00000422330.5	TSL:4	c.-89+91868G>A		intron	N/A	ENSP00000408594.1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86614 AN: 151876 Hom.: 25987 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.611

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

GnomAD4 genome AF: 0.570 AC: 86683 AN: 151996 Hom.: 26015 Cov.: 32 AF XY: 0.561 AC XY: 41696 AN XY: 74264

African (AFR) AF: 0.428 AC: 17723 AN: 41442

American (AMR) AF: 0.619 AC: 9453 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2481 AN: 3472

East Asian (EAS) AF: 0.217 AC: 1120 AN: 5156

South Asian (SAS) AF: 0.413 AC: 1990 AN: 4818

European-Finnish (FIN) AF: 0.591 AC: 6222 AN: 10528

Middle Eastern (MID) AF: 0.592 AC: 173 AN: 292

European-Non Finnish (NFE) AF: 0.671 AC: 45650 AN: 67994

Other (OTH) AF: 0.605 AC: 1280 AN: 2114

Alfa AF: 0.635 Hom.: 15855

Bravo AF: 0.568

Asia WGS AF: 0.336 AC: 1172 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.27
DANN	Benign	0.43
PhyloP100		0.12
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: rs2134358; hg19: chr3-2472785;