Genetic Variant CNTNAP5:c.1877-33C>T (chr2-124647725-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.283

Publications

8 publications found

Variant links:

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

CNTNAP5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

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.1877-33C>T		intron	N/A	NP_001354427.1	A0A804HKY0
	CNTNAP5	NM_130773.4		c.1874-33C>T		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.1877-33C>T		intron	N/A	ENSP00000508115.1	A0A804HKY0
	CNTNAP5	ENST00000431078.1	TSL:1	c.1874-33C>T		intron	N/A	ENSP00000399013.1	Q8WYK1

Frequencies

GnomAD3 genomes

AF:

0.505

AC:

76744

AN:

151992

Hom.:

20684

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.584

AC XY:

396540

AN XY:

678852

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

16950

33900

50851

67801

84751

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18102

36204

54306

72408

90510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.505

AC:

76798

AN:

152110

Hom.:

20698

Cov.:

AF XY:

0.502

AC XY:

37347

AN XY:

74366

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1875

3751

5626

7502

9377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

682

1364

2046

2728

3410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.033

(source)

DANN

Benign

0.56

PhyloP100

-0.28

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over