rs4485401

Positions:

• chr16-76532260-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033401.5(CNTNAP4):​c.2756-3285A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 152,020 control chromosomes in the GnomAD database, including 13,994 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 0.42 (13994 hom., cov: 32)
• Consequence: CNTNAP4 NM_033401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185

Genes affected

CNTNAP4 (HGNC:18747): (contactin associated protein family member 4) This gene encodes a member of the neurexin protein family. Members of this family function in the vertebrate nervous system as cell adhesion molecules and receptors. This protein contains epidermal growth factor repeats and laminin G domains. In addition, it includes an F5/8 type C domain, discoidin/neuropilin- and fibrinogen-like domains, and thrombospondin N-terminal-like domains. This protein may also play a role in proper neurotransmission in the dopaminergic and GABAergic systems and mutations in this gene may be associated with certain psychiatric illnesses. A polymorphism in an intron of this gene may be associated with longevity. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP4	NM_033401.5	c.2756-3285A>G		intron_variant		ENST00000611870.5	NP_207837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTNAP4	ENST00000611870.5	c.2756-3285A>G		intron_variant		1	NM_033401.5	ENSP00000479811	P4

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64243 AN: 151900 Hom.: 13986 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.423 AC: 64289 AN: 152020 Hom.: 13994 Cov.: 32 AF XY: 0.425 AC XY: 31563 AN XY: 74318

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.529

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.458

Alfa AF: 0.453 Hom.: 29252

Bravo AF: 0.420

Asia WGS AF: 0.509 AC: 1769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.36

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: rs4485401; hg19: chr16-76566157;