2-124524333-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001367498.1(CNTNAP5):c.1358C>T(p.Ser453Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0408 in 1,613,644 control chromosomes in the GnomAD database, including 1,554 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.034 ( 130 hom., cov: 32)

Exomes 𝑓: 0.041 ( 1424 hom. )

Consequence

CNTNAP5
NM_001367498.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.85

Publications

24 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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045080483).

BP6

Variant 2-124524333-C-T is Benign according to our data. Variant chr2-124524333-C-T is described in ClinVar as Benign. ClinVar VariationId is 3056463.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0342 (5201/152174) while in subpopulation NFE AF = 0.0458 (3113/68006). AF 95% confidence interval is 0.0444. There are 130 homozygotes in GnomAd4. There are 2715 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 130 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
CNTNAP5	NM_001367498.1 link	c.1358C>T	p.Ser453Leu	missense_variant	Exon 9 of 24	ENST00000682447.1	NP_001354427.1
CNTNAP5	NM_130773.4 link	c.1355C>T	p.Ser452Leu	missense_variant	Exon 9 of 24		NP_570129.1
CNTNAP5	XM_017003316.2 link	c.1358C>T	p.Ser453Leu	missense_variant	Exon 9 of 23		XP_016858805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP5	ENST00000682447.1 link	c.1358C>T	p.Ser453Leu	missense_variant	Exon 9 of 24		NM_001367498.1	ENSP00000508115.1
CNTNAP5	ENST00000431078.1 link	c.1355C>T	p.Ser452Leu	missense_variant	Exon 9 of 24	1		ENSP00000399013.1

Frequencies

GnomAD3 genomes

AF:

0.0342

AC:

5206

AN:

152058

Hom.:

130

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00667

Gnomad AMI

AF:

0.0779

Gnomad AMR

AF:

0.0289

Gnomad ASJ

AF:

0.0464

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.0149

Gnomad FIN

AF:

0.0903

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0458

Gnomad OTH

AF:

0.0483

GnomAD2 exomes

AF:

0.0360

AC:

8958

AN:

248590

AF XY:

0.0364

show subpopulations

Gnomad AFR exome

AF:

0.00484

Gnomad AMR exome

AF:

0.0186

Gnomad ASJ exome

AF:

0.0504

Gnomad EAS exome

AF:

0.000279

Gnomad FIN exome

AF:

0.0841

Gnomad NFE exome

AF:

0.0466

Gnomad OTH exome

AF:

0.0341

GnomAD4 exome

AF:

0.0415

AC:

60635

AN:

1461470

Hom.:

1424

Cov.:

AF XY:

0.0413

AC XY:

30058

AN XY:

727016

show subpopulations

African (AFR)

AF:

0.00663

AC:

222

AN:

33476

American (AMR)

AF:

0.0199

AC:

892

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0487

AC:

1272

AN:

26134

East Asian (EAS)

AF:

0.000227

AC:

AN:

39670

South Asian (SAS)

AF:

0.0164

AC:

1413

AN:

86250

European-Finnish (FIN)

AF:

0.0810

AC:

4322

AN:

53390

Middle Eastern (MID)

AF:

0.0335

AC:

193

AN:

5766

European-Non Finnish (NFE)

AF:

0.0450

AC:

50069

AN:

1111704

Other (OTH)

AF:

0.0372

AC:

2243

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

2923

5846

8768

11691

14614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1816

3632

5448

7264

9080

<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:

0.0342

AC:

5201

AN:

152174

Hom.:

130

Cov.:

AF XY:

0.0365

AC XY:

2715

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.00667

AC:

277

AN:

41520

American (AMR)

AF:

0.0289

AC:

441

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0464

AC:

161

AN:

3470

East Asian (EAS)

AF:

0.000774

AC:

AN:

5168

South Asian (SAS)

AF:

0.0143

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0903

AC:

956

AN:

10588

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0458

AC:

3113

AN:

68006

Other (OTH)

AF:

0.0473

AC:

100

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

265

530

796

1061

1326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.0401

Hom.:

463

Bravo

AF:

0.0285

TwinsUK

AF:

0.0437

AC:

162

ALSPAC

AF:

0.0405

AC:

156

ESP6500AA

AF:

0.00553

AC:

ESP6500EA

AF:

0.0509

AC:

429

ExAC

AF:

0.0339

AC:

4107

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.0500

EpiControl

AF:

0.0503

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CNTNAP5-related disorder

Benign:1

May 02, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

Eigen

Benign

-0.049

Eigen_PC

Benign

0.070

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0045

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.6

PhyloP100

1.8

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-4.8

REVEL

Benign

0.28

Sift

Benign

0.048

Sift4G

Uncertain

0.057

Vest4

0.090

ClinPred

0.041

GERP RS

6.0

Varity_R

0.49

gMVP

0.77

Mutation Taster

=88/12

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over