rs724655

Variant names:

• chr2-124762886-T-G
• rs724655
• NM_001367498.1:c.2235-786T>G

Variant summary

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

The NM_001367498.1(CNTNAP5):​c.2235-786T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,560 control chromosomes in the GnomAD database, including 14,588 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 0.43 (14588 hom., cov: 29)
• Consequence: CNTNAP5 NM_001367498.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.524 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.2235-786T>G		intron	N/A	NP_001354427.1	A0A804HKY0
	CNTNAP5	NM_130773.4		c.2232-786T>G		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.2235-786T>G		intron	N/A	ENSP00000508115.1	A0A804HKY0
	CNTNAP5	ENST00000431078.1	TSL:1	c.2232-786T>G		intron	N/A	ENSP00000399013.1	Q8WYK1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64401 AN: 151444 Hom.: 14569 Cov.: 29

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.425 AC: 64465 AN: 151560 Hom.: 14588 Cov.: 29 AF XY: 0.413 AC XY: 30541 AN XY: 74022

African (AFR) AF: 0.324 AC: 13371 AN: 41300

American (AMR) AF: 0.419 AC: 6365 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1230 AN: 3462

East Asian (EAS) AF: 0.160 AC: 819 AN: 5134

South Asian (SAS) AF: 0.258 AC: 1236 AN: 4800

European-Finnish (FIN) AF: 0.393 AC: 4133 AN: 10526

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35837 AN: 67838

Other (OTH) AF: 0.451 AC: 948 AN: 2104

Alfa AF: 0.488 Hom.: 9537

Bravo AF: 0.424

Asia WGS AF: 0.254 AC: 886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.47
PhyloP100		0.55
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: rs724655; hg19: chr2-125520463;