Variant 2-124524333-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 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 criteria provided, single submitter B:1

Conservation

PhyloP100: 1.85

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 130 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CNTNAP5	NM_001367498.1 linkuse as main transcript	c.1358C>T	p.Ser453Leu	missense_variant	9/24	ENST00000682447.1
CNTNAP5	NM_130773.4 linkuse as main transcript	c.1355C>T	p.Ser452Leu	missense_variant	9/24
CNTNAP5	XM_017003316.2 linkuse as main transcript	c.1358C>T	p.Ser453Leu	missense_variant	9/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTNAP5	ENST00000682447.1 linkuse as main transcript	c.1358C>T	p.Ser453Leu	missense_variant	9/24		NM_001367498.1	A1
CNTNAP5	ENST00000431078.1 linkuse as main transcript	c.1355C>T	p.Ser452Leu	missense_variant	9/24	1		P4

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

GnomAD3 exomes

AF:

0.0360

AC:

8958

AN:

248590

Hom.:

250

AF XY:

0.0364

AC XY:

4910

AN XY:

134826

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 SAS exome

AF:

0.0153

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

Gnomad4 AFR exome

AF:

0.00663

Gnomad4 AMR exome

AF:

0.0199

Gnomad4 ASJ exome

AF:

0.0487

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0164

Gnomad4 FIN exome

AF:

0.0810

Gnomad4 NFE exome

AF:

0.0450

Gnomad4 OTH exome

AF:

0.0372

GnomAD4 genome

AF:

0.0342

AC:

5201

AN:

152174

Hom.:

130

Cov.:

AF XY:

0.0365

AC XY:

2715

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.00667

Gnomad4 AMR

AF:

0.0289

Gnomad4 ASJ

AF:

0.0464

Gnomad4 EAS

AF:

0.000774

Gnomad4 SAS

AF:

0.0143

Gnomad4 FIN

AF:

0.0903

Gnomad4 NFE

AF:

0.0458

Gnomad4 OTH

AF:

0.0473

Alfa

AF:

0.0423

Hom.:

337

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: criteria provided, single submitter

LINK: link

Submissions by phenotype

CNTNAP5-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 02, 2019

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

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

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-4.8

REVEL

Benign

0.28

Sift

Benign

0.048

Sift4G

Uncertain

0.057

Polyphen

0.011

Vest4

0.090

MPC

0.077

ClinPred

0.041

GERP RS

6.0

Varity_R

0.49

gMVP

0.77

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over