chr2-124637218-G-A

Variant names:

• chr2-124637218-G-A
• rs11900792
• NM_001367498.1:c.1877-10540G>A

Variant summary

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

The NM_001367498.1(CNTNAP5):​c.1877-10540G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 151,990 control chromosomes in the GnomAD database, including 3,548 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 (3548 hom., cov: 32)
• Consequence: CNTNAP5 NM_001367498.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP5	NM_001367498.1	c.1877-10540G>A		intron_variant	Intron 12 of 23	ENST00000682447.1	NP_001354427.1
CNTNAP5	NM_130773.4	c.1874-10540G>A		intron_variant	Intron 12 of 23		NP_570129.1
CNTNAP5	XM_017003316.2	c.1877-10540G>A		intron_variant	Intron 12 of 22		XP_016858805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP5	ENST00000682447.1	c.1877-10540G>A		intron_variant	Intron 12 of 23		NM_001367498.1	ENSP00000508115.1
CNTNAP5	ENST00000431078.1	c.1874-10540G>A		intron_variant	Intron 12 of 23	1		ENSP00000399013.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25134 AN: 151874 Hom.: 3549 Cov.: 32

Gnomad AFR AF: 0.0420

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.165 AC: 25134 AN: 151990 Hom.: 3548 Cov.: 32 AF XY: 0.176 AC XY: 13091 AN XY: 74268

African (AFR) AF: 0.0419 AC: 1738 AN: 41494

American (AMR) AF: 0.291 AC: 4442 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 703 AN: 3468

East Asian (EAS) AF: 0.720 AC: 3722 AN: 5168

South Asian (SAS) AF: 0.339 AC: 1629 AN: 4810

European-Finnish (FIN) AF: 0.172 AC: 1808 AN: 10510

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10572 AN: 67970

Other (OTH) AF: 0.179 AC: 377 AN: 2108

Alfa AF: 0.149 Hom.: 3203

Bravo AF: 0.167

Asia WGS AF: 0.490 AC: 1700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.38
DANN	Benign	0.44
PhyloP100		-2.3
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: rs11900792; hg19: chr2-125394795;