rs6564350

Variant names:

• chr16-76547705-G-A
• rs6564350
• NM_033401.5:c.3443-5578G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_033401.5(CNTNAP4):​c.3443-5578G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,054 control chromosomes in the GnomAD database, including 7,788 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 0.32 (7788 hom., cov: 32)
• Consequence: CNTNAP4 NM_033401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.673
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP4	NM_033401.5	c.3443-5578G>A		intron_variant	Intron 21 of 23	ENST00000611870.5	NP_207837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP4	ENST00000611870.5	c.3443-5578G>A		intron_variant	Intron 21 of 23	1	NM_033401.5	ENSP00000479811.1
ENSG00000287694	ENST00000655556.1	n.3443-5578G>A		intron_variant	Intron 21 of 24			ENSP00000499374.1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47891 AN: 151936 Hom.: 7773 Cov.: 32

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.315 AC: 47937 AN: 152054 Hom.: 7788 Cov.: 32 AF XY: 0.313 AC XY: 23254 AN XY: 74310

African (AFR) AF: 0.400 AC: 16577 AN: 41480

American (AMR) AF: 0.240 AC: 3666 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 793 AN: 3472

East Asian (EAS) AF: 0.339 AC: 1748 AN: 5158

South Asian (SAS) AF: 0.357 AC: 1723 AN: 4822

European-Finnish (FIN) AF: 0.255 AC: 2686 AN: 10552

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19925 AN: 67974

Other (OTH) AF: 0.266 AC: 561 AN: 2106

Alfa AF: 0.295 Hom.: 21875

Bravo AF: 0.314

Asia WGS AF: 0.391 AC: 1362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	13
DANN	Benign	0.82
PhyloP100		0.67
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: rs6564350; hg19: chr16-76581602;