rs6706476

Variant names:

• chr2-124487230-G-C
• rs6706476
• NM_001367498.1:c.1062+12348G>C

Variant summary

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

The NM_001367498.1(CNTNAP5):​c.1062+12348G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,026 control chromosomes in the GnomAD database, including 2,806 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 0.17 (2806 hom., cov: 32)
• Consequence: CNTNAP5 NM_001367498.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570
• Publications: 2 publications found

Genes affected

CNTNAP5 (HGNC:18748): (contactin associated protein family member 5) This gene product belongs to the neurexin family, members of which function in the vertebrate nervous system as cell adhesion molecules and receptors. This protein, like other neurexin proteins, 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. [provided by RefSeq, Jul 2008]

CNTNAP5 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367498.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP5	NM_001367498.1	MANE Select	c.1062+12348G>C		intron	N/A	NP_001354427.1	A0A804HKY0
	CNTNAP5	NM_130773.4		c.1059+12351G>C		intron	N/A	NP_570129.1	Q8WYK1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP5	ENST00000682447.1	MANE Select	c.1062+12348G>C		intron	N/A	ENSP00000508115.1	A0A804HKY0
	CNTNAP5	ENST00000431078.1	TSL:1	c.1059+12351G>C		intron	N/A	ENSP00000399013.1	Q8WYK1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25299 AN: 151908 Hom.: 2799 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.0978

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.128

Gnomad NFE AF: 0.0858

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.167 AC: 25344 AN: 152026 Hom.: 2806 Cov.: 32 AF XY: 0.171 AC XY: 12684 AN XY: 74310

African (AFR) AF: 0.299 AC: 12401 AN: 41458

American (AMR) AF: 0.189 AC: 2884 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0978 AC: 339 AN: 3466

East Asian (EAS) AF: 0.159 AC: 818 AN: 5152

South Asian (SAS) AF: 0.256 AC: 1233 AN: 4812

European-Finnish (FIN) AF: 0.134 AC: 1419 AN: 10566

Middle Eastern (MID) AF: 0.128 AC: 37 AN: 290

European-Non Finnish (NFE) AF: 0.0858 AC: 5833 AN: 67986

Other (OTH) AF: 0.147 AC: 309 AN: 2106

Alfa AF: 0.126 Hom.: 208

Bravo AF: 0.175

Asia WGS AF: 0.217 AC: 751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.56
PhyloP100		0.057
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: rs6706476; hg19: chr2-125244807;