rs1428758

Positions:

• chr16-76307609-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.86-8804A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 148,648 control chromosomes in the GnomAD database, including 7,678 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 0.30 (7678 hom., cov: 28)
• Consequence: CNTNAP4 NM_033401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175

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]

ENSG00000287694 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP4	NM_033401.5	c.86-8804A>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.86-8804A>G		intron_variant		1	NM_033401.5	ENSP00000479811.1
ENSG00000287694	ENST00000655556.1	n.86-8804A>G		intron_variant				ENSP00000499374.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 44791 AN: 148586 Hom.: 7674 Cov.: 28

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.0109

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.301 AC: 44817 AN: 148648 Hom.: 7678 Cov.: 28 AF XY: 0.297 AC XY: 21498 AN XY: 72310

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.0109

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.282

Alfa AF: 0.357 Hom.: 13076

Bravo AF: 0.283

Asia WGS AF: 0.132 AC: 460 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.036
DANN	Benign	0.54

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: rs1428758; hg19: chr16-76341506;