2-124647725-C-T

Variant names:

• chr2-124647725-C-T
• rs924802
• NM_001367498.1:c.1877-33C>T

Variant summary

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

The NM_001367498.1(CNTNAP5):​c.1877-33C>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
• Publications: 8 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=-0.83).
• 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 rank	MANE	Protein	UniProt
CNTNAP5	NM_001367498.1	c.1877-33C>T		intron_variant	Intron 12 of 23	ENST00000682447.1	NP_001354427.1
CNTNAP5	NM_130773.4	c.1874-33C>T		intron_variant	Intron 12 of 23		NP_570129.1
CNTNAP5	XM_017003316.2	c.1877-33C>T		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.1877-33C>T		intron_variant	Intron 12 of 23		NM_001367498.1	ENSP00000508115.1
CNTNAP5	ENST00000431078.1	c.1874-33C>T		intron_variant	Intron 12 of 23	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

GnomAD2 exomes AF: 0.517 AC: 100226 AN: 193696 AF XY: 0.524

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 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

African (AFR) AF: 0.340 AC: 10733 AN: 31550

American (AMR) AF: 0.427 AC: 15196 AN: 35624

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 10757 AN: 21708

East Asian (EAS) AF: 0.215 AC: 8287 AN: 38458

South Asian (SAS) AF: 0.500 AC: 37845 AN: 75710

European-Finnish (FIN) AF: 0.619 AC: 31312 AN: 50564

Middle Eastern (MID) AF: 0.545 AC: 2948 AN: 5408

European-Non Finnish (NFE) AF: 0.620 AC: 662270 AN: 1067624

Other (OTH) AF: 0.555 AC: 31586 AN: 56914

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

African (AFR) AF: 0.353 AC: 14628 AN: 41482

American (AMR) AF: 0.461 AC: 7047 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1754 AN: 3470

East Asian (EAS) AF: 0.216 AC: 1116 AN: 5164

South Asian (SAS) AF: 0.479 AC: 2312 AN: 4826

European-Finnish (FIN) AF: 0.615 AC: 6508 AN: 10586

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.617 AC: 41930 AN: 67980

Other (OTH) AF: 0.504 AC: 1064 AN: 2112

Alfa AF: 0.569 Hom.: 80413

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
PhyloP100		-0.28
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: rs924802; hg19: chr2-125405302; COSMIC: COSV70478620;