Variant summary

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

The NM_001367498.1(CNTNAP5):c.3587C>T(p.Thr1196Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 1,607,612 control chromosomes in the GnomAD database, including 393 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.015 ( 32 hom., cov: 32)

Exomes 𝑓: 0.021 ( 361 hom. )

Consequence

CNTNAP5
NM_001367498.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0740

Publications

10 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=0.0028316975).

BP6

Variant 2-124903032-C-T is Benign according to our data. Variant chr2-124903032-C-T is described in ClinVar as Benign. ClinVar VariationId is 3056415.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.015 (2287/152216) while in subpopulation NFE AF = 0.0235 (1597/67994). AF 95% confidence interval is 0.0225. There are 32 homozygotes in GnomAd4. There are 1003 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 32 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP5	NM_001367498.1	MANE Select	c.3587C>T	p.Thr1196Met	missense	Exon 22 of 24	NP_001354427.1
	CNTNAP5	NM_130773.4		c.3584C>T	p.Thr1195Met	missense	Exon 22 of 24	NP_570129.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP5	ENST00000682447.1	MANE Select	c.3587C>T	p.Thr1196Met	missense	Exon 22 of 24	ENSP00000508115.1
	CNTNAP5	ENST00000431078.1	TSL:1	c.3584C>T	p.Thr1195Met	missense	Exon 22 of 24	ENSP00000399013.1

Frequencies

GnomAD3 genomes

AF:

0.0150

AC:

2285

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00613

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.0116

Gnomad ASJ

AF:

0.0222

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.00330

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0235

Gnomad OTH

AF:

0.0163

GnomAD2 exomes

AF:

0.0154

AC:

3661

AN:

237804

AF XY:

0.0165

show subpopulations

Gnomad AFR exome

AF:

0.00516

Gnomad AMR exome

AF:

0.00891

Gnomad ASJ exome

AF:

0.0249

Gnomad EAS exome

AF:

0.000117

Gnomad FIN exome

AF:

0.00443

Gnomad NFE exome

AF:

0.0222

Gnomad OTH exome

AF:

0.0204

GnomAD4 exome

AF:

0.0208

AC:

30229

AN:

1455396

Hom.:

361

Cov.:

AF XY:

0.0210

AC XY:

15164

AN XY:

723376

show subpopulations

African (AFR)

AF:

0.00434

AC:

145

AN:

33386

American (AMR)

AF:

0.00981

AC:

431

AN:

43916

Ashkenazi Jewish (ASJ)

AF:

0.0263

AC:

683

AN:

25982

East Asian (EAS)

AF:

0.0000509

AC:

AN:

39274

South Asian (SAS)

AF:

0.0164

AC:

1397

AN:

85154

European-Finnish (FIN)

AF:

0.00501

AC:

266

AN:

53052

Middle Eastern (MID)

AF:

0.0203

AC:

117

AN:

5756

European-Non Finnish (NFE)

AF:

0.0235

AC:

26034

AN:

1108732

Other (OTH)

AF:

0.0192

AC:

1154

AN:

60144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

1423

2846

4268

5691

7114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

968

1936

2904

3872

4840

<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:

0.0150

AC:

2287

AN:

152216

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

1003

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.00611

AC:

254

AN:

41556

American (AMR)

AF:

0.0116

AC:

177

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0222

AC:

AN:

3468

East Asian (EAS)

AF:

0.000194

AC:

AN:

5150

South Asian (SAS)

AF:

0.0124

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00330

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0235

AC:

1597

AN:

67994

Other (OTH)

AF:

0.0161

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

114

227

341

454

568

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0199

Hom.:

106

Bravo

AF:

0.0155

TwinsUK

AF:

0.0243

AC:

ALSPAC

AF:

0.0244

AC:

ESP6500AA

AF:

0.00518

AC:

ESP6500EA

AF:

0.0243

AC:

207

ExAC

AF:

0.0148

AC:

1790

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

CNTNAP5-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

3.8

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.074

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0028

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.8

PhyloP100

-0.074

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.2

REVEL

Benign

0.23

Sift

Benign

0.039

Sift4G

Uncertain

0.031

Polyphen

0.0050

Vest4

0.052

MPC

0.088

ClinPred

0.015

GERP RS

-5.5

Varity_R

0.028

gMVP

0.40

Mutation Taster

=91/9

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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NM_001367498.1:c.3587C>T

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over