16-76446247-C-G

Variant names:

• chr16-76446247-C-G
• rs6564337
• NM_033401.5:c.539-1765C>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.539-1765C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 152,056 control chromosomes in the GnomAD database, including 29,918 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 0.63 (29918 hom., cov: 33)
• Consequence: CNTNAP4 NM_033401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.95
• Publications: 1 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=-0.54).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP4	NM_033401.5	c.539-1765C>G		intron_variant	Intron 4 of 23	ENST00000611870.5	NP_207837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP4	ENST00000611870.5	c.539-1765C>G		intron_variant	Intron 4 of 23	1	NM_033401.5	ENSP00000479811.1
ENSG00000287694	ENST00000655556.1	n.539-1765C>G		intron_variant	Intron 4 of 24			ENSP00000499374.1

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94977 AN: 151936 Hom.: 29892 Cov.: 33

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.637

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

GnomAD4 genome AF: 0.625 AC: 95057 AN: 152056 Hom.: 29918 Cov.: 33 AF XY: 0.624 AC XY: 46381 AN XY: 74308

African (AFR) AF: 0.699 AC: 29010 AN: 41484

American (AMR) AF: 0.591 AC: 9025 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2055 AN: 3470

East Asian (EAS) AF: 0.565 AC: 2912 AN: 5156

South Asian (SAS) AF: 0.708 AC: 3418 AN: 4828

European-Finnish (FIN) AF: 0.586 AC: 6188 AN: 10568

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.593 AC: 40316 AN: 67974

Other (OTH) AF: 0.639 AC: 1348 AN: 2108

Alfa AF: 0.611 Hom.: 3573

Bravo AF: 0.624

Asia WGS AF: 0.698 AC: 2423 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.49
PhyloP100		3.0
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: rs6564337; hg19: chr16-76480144;