16-76532260-A-G

Variant names:

• chr16-76532260-A-G
• rs4485401
• NM_033401.5:c.2756-3285A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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 -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 rank	MANE	Protein	UniProt
CNTNAP4	NM_033401.5	c.2756-3285A>G		intron_variant	Intron 17 of 23	ENST00000611870.5	NP_207837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP4	ENST00000611870.5	c.2756-3285A>G		intron_variant	Intron 17 of 23	1	NM_033401.5	ENSP00000479811.1
ENSG00000287694	ENST00000655556.1	n.2756-3285A>G		intron_variant	Intron 17 of 24			ENSP00000499374.1

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

African (AFR) AF: 0.317 AC: 13137 AN: 41466

American (AMR) AF: 0.461 AC: 7032 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1778 AN: 3472

East Asian (EAS) AF: 0.529 AC: 2724 AN: 5152

South Asian (SAS) AF: 0.553 AC: 2662 AN: 4816

European-Finnish (FIN) AF: 0.438 AC: 4623 AN: 10566

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30700 AN: 67964

Other (OTH) AF: 0.458 AC: 968 AN: 2114

Alfa AF: 0.447 Hom.: 60630

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
PhyloP100		0.18
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: rs4485401; hg19: chr16-76566157;