16-76547936-A-G

Variant names:

• chr16-76547936-A-G
• rs7187962
• NM_033401.5:c.3443-5347A>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.3443-5347A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,118 control chromosomes in the GnomAD database, including 8,108 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 0.32 (8108 hom., cov: 32)
• Consequence: CNTNAP4 NM_033401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP4	NM_033401.5	c.3443-5347A>G		intron_variant	Intron 21 of 23	ENST00000611870.5	NP_207837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP4	ENST00000611870.5	c.3443-5347A>G		intron_variant	Intron 21 of 23	1	NM_033401.5	ENSP00000479811.1
ENSG00000287694	ENST00000655556.1	n.3443-5347A>G		intron_variant	Intron 21 of 24			ENSP00000499374.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48682 AN: 152000 Hom.: 8093 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.320 AC: 48729 AN: 152118 Hom.: 8108 Cov.: 32 AF XY: 0.318 AC XY: 23644 AN XY: 74374

African (AFR) AF: 0.417 AC: 17306 AN: 41474

American (AMR) AF: 0.241 AC: 3680 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 793 AN: 3472

East Asian (EAS) AF: 0.340 AC: 1756 AN: 5162

South Asian (SAS) AF: 0.358 AC: 1726 AN: 4826

European-Finnish (FIN) AF: 0.255 AC: 2706 AN: 10592

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19936 AN: 67984

Other (OTH) AF: 0.270 AC: 570 AN: 2114

Alfa AF: 0.317 Hom.: 985

Bravo AF: 0.320

Asia WGS AF: 0.393 AC: 1367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.1
DANN	Benign	0.67
PhyloP100		-0.018
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: rs7187962; hg19: chr16-76581833;