16-76491731-A-G

Position:

• chr16-76491731-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.2080+1848A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,184 control chromosomes in the GnomAD database, including 50,247 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 0.80 (50247 hom., cov: 32)
• Consequence: CNTNAP4 NM_033401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP4	NM_033401.5	c.2080+1848A>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.2080+1848A>G		intron_variant		1	NM_033401.5	ENSP00000479811.1
ENSG00000287694	ENST00000655556.1	n.2080+1848A>G		intron_variant				ENSP00000499374.1

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121813 AN: 152066 Hom.: 50226 Cov.: 32

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.894

Gnomad AMR AF: 0.881

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 0.962

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.889

Gnomad OTH AF: 0.836

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

GnomAD4 genome AF: 0.801 AC: 121872 AN: 152184 Hom.: 50247 Cov.: 32 AF XY: 0.801 AC XY: 59568 AN XY: 74382

Gnomad4 AFR AF: 0.580

Gnomad4 AMR AF: 0.881

Gnomad4 ASJ AF: 0.941

Gnomad4 EAS AF: 0.962

Gnomad4 SAS AF: 0.846

Gnomad4 FIN AF: 0.820

Gnomad4 NFE AF: 0.889

Gnomad4 OTH AF: 0.833

Alfa AF: 0.794 Hom.: 6696

Bravo AF: 0.797

Asia WGS AF: 0.851 AC: 2962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.6
DANN	Benign	0.70

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: rs4888514; hg19: chr16-76525628;