16-76404749-G-T

Variant names:

• chr16-76404749-G-T
• rs6564329
• NM_033401.5:c.391-22703G>T

Variant summary

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

The NM_033401.5(CNTNAP4):​c.391-22703G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 152,098 control chromosomes in the GnomAD database, including 54,032 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 0.84 (54032 hom., cov: 32)
• Consequence: CNTNAP4 NM_033401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP4	NM_033401.5	c.391-22703G>T		intron_variant	Intron 3 of 23	ENST00000611870.5	NP_207837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP4	ENST00000611870.5	c.391-22703G>T		intron_variant	Intron 3 of 23	1	NM_033401.5	ENSP00000479811.1
ENSG00000287694	ENST00000655556.1	n.391-22703G>T		intron_variant	Intron 3 of 24			ENSP00000499374.1

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127868 AN: 151980 Hom.: 54003 Cov.: 32

Gnomad AFR AF: 0.870

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.844

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.837

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

GnomAD4 genome AF: 0.841 AC: 127951 AN: 152098 Hom.: 54032 Cov.: 32 AF XY: 0.837 AC XY: 62242 AN XY: 74324

African (AFR) AF: 0.870 AC: 36115 AN: 41522

American (AMR) AF: 0.811 AC: 12384 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.872 AC: 3028 AN: 3472

East Asian (EAS) AF: 0.634 AC: 3279 AN: 5172

South Asian (SAS) AF: 0.696 AC: 3354 AN: 4818

European-Finnish (FIN) AF: 0.850 AC: 8982 AN: 10572

Middle Eastern (MID) AF: 0.843 AC: 241 AN: 286

European-Non Finnish (NFE) AF: 0.854 AC: 58041 AN: 67954

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

Alfa AF: 0.852 Hom.: 42917

Bravo AF: 0.841

Asia WGS AF: 0.648 AC: 2239 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.1
DANN	Benign	0.55
PhyloP100		-0.11
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: rs6564329; hg19: chr16-76438646;