16-76491731-A-G

Variant names:

• chr16-76491731-A-G
• rs4888514
• NM_033401.5:c.2080+1848A>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.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
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033401.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP4	NM_033401.5	MANE Select	c.2080+1848A>G		intron	N/A	NP_207837.2
	CNTNAP4	NM_001322181.2		c.2077+1848A>G		intron	N/A	NP_001309110.1
	CNTNAP4	NM_001322188.2		c.2080+1848A>G		intron	N/A	NP_001309117.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP4	ENST00000611870.5	TSL:1 MANE Select	c.2080+1848A>G		intron	N/A	ENSP00000479811.1
	CNTNAP4	ENST00000622250.4	TSL:1	c.1936+1848A>G		intron	N/A	ENSP00000477698.1
	ENSG00000287694	ENST00000655556.1		n.2080+1848A>G		intron	N/A	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

African (AFR) AF: 0.580 AC: 24051 AN: 41480

American (AMR) AF: 0.881 AC: 13485 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.941 AC: 3266 AN: 3472

East Asian (EAS) AF: 0.962 AC: 4980 AN: 5176

South Asian (SAS) AF: 0.846 AC: 4077 AN: 4822

European-Finnish (FIN) AF: 0.820 AC: 8693 AN: 10598

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.889 AC: 60482 AN: 68014

Other (OTH) AF: 0.833 AC: 1762 AN: 2116

Alfa AF: 0.786 Hom.: 6830

Bravo AF: 0.797

Asia WGS AF: 0.851 AC: 2962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.6
DANN	Benign	0.70
PhyloP100		-0.31
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: rs4888514; hg19: chr16-76525628;