chr2-124647725-C-T

Position:

• chr2-124647725-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367498.1(CNTNAP5):​c.1877-33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 1,535,670 control chromosomes in the GnomAD database, including 264,087 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 0.50 (20698 hom., cov: 33)
  • Exomes 𝑓: 0.59 (243389 hom.)
• Consequence: CNTNAP5 NM_001367498.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP5	NM_001367498.1	c.1877-33C>T		intron_variant		ENST00000682447.1	NP_001354427.1
CNTNAP5	NM_130773.4	c.1874-33C>T		intron_variant			NP_570129.1
CNTNAP5	XM_017003316.2	c.1877-33C>T		intron_variant			XP_016858805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTNAP5	ENST00000682447.1	c.1877-33C>T		intron_variant			NM_001367498.1	ENSP00000508115.1
CNTNAP5	ENST00000431078.1	c.1874-33C>T		intron_variant		1		ENSP00000399013.1

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76744 AN: 151992 Hom.: 20684 Cov.: 33

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.505

GnomAD3 exomes AF: 0.517 AC: 100226 AN: 193696 Hom.: 27336 AF XY: 0.524 AC XY: 54338 AN XY: 103656

Gnomad AFR exome AF: 0.349

Gnomad AMR exome AF: 0.424

Gnomad ASJ exome AF: 0.484

Gnomad EAS exome AF: 0.214

Gnomad SAS exome AF: 0.495

Gnomad FIN exome AF: 0.621

Gnomad NFE exome AF: 0.610

Gnomad OTH exome AF: 0.525

GnomAD4 exome AF: 0.586 AC: 810934 AN: 1383560 Hom.: 243389 Cov.: 30 AF XY: 0.584 AC XY: 396540 AN XY: 678852

Gnomad4 AFR exome AF: 0.340

Gnomad4 AMR exome AF: 0.427

Gnomad4 ASJ exome AF: 0.496

Gnomad4 EAS exome AF: 0.215

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.619

Gnomad4 NFE exome AF: 0.620

Gnomad4 OTH exome AF: 0.555

GnomAD4 genome AF: 0.505 AC: 76798 AN: 152110 Hom.: 20698 Cov.: 33 AF XY: 0.502 AC XY: 37347 AN XY: 74366

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.504

Alfa AF: 0.583 Hom.: 54713

Bravo AF: 0.487

Asia WGS AF: 0.360 AC: 1257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.033
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs924802; hg19: chr2-125405302; COSMIC: COSV70478620;