16-76284645-G-C

Variant names:

• chr16-76284645-G-C
• rs7193230
• NM_033401.5:c.85+6898G>C

Variant summary

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

The NM_033401.5(CNTNAP4):​c.85+6898G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 151,924 control chromosomes in the GnomAD database, including 46,257 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 0.78 (46257 hom., cov: 32)
• Consequence: CNTNAP4 NM_033401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP4	NM_033401.5	c.85+6898G>C		intron_variant	Intron 1 of 23	ENST00000611870.5	NP_207837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP4	ENST00000611870.5	c.85+6898G>C		intron_variant	Intron 1 of 23	1	NM_033401.5	ENSP00000479811.1
ENSG00000287694	ENST00000655556.1	n.85+6898G>C		intron_variant	Intron 1 of 24			ENSP00000499374.1

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117623 AN: 151806 Hom.: 46198 Cov.: 32

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.725

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

GnomAD4 genome AF: 0.775 AC: 117744 AN: 151924 Hom.: 46257 Cov.: 32 AF XY: 0.776 AC XY: 57616 AN XY: 74268

African (AFR) AF: 0.906 AC: 37612 AN: 41530

American (AMR) AF: 0.784 AC: 11951 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2424 AN: 3464

East Asian (EAS) AF: 0.746 AC: 3851 AN: 5162

South Asian (SAS) AF: 0.631 AC: 3047 AN: 4828

European-Finnish (FIN) AF: 0.756 AC: 7993 AN: 10570

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.716 AC: 48576 AN: 67808

Other (OTH) AF: 0.724 AC: 1527 AN: 2110

Alfa AF: 0.652 Hom.: 1836

Bravo AF: 0.784

Asia WGS AF: 0.687 AC: 2385 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	0.68
DANN	Benign	0.39
PhyloP100		-0.36
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: rs7193230; hg19: chr16-76318542;