2-124903032-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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 made for transcript

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

BS2

High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP5	NM_001367498.1 link	c.3587C>T	p.Thr1196Met	missense_variant	Exon 22 of 24	ENST00000682447.1	NP_001354427.1
CNTNAP5	NM_130773.4 link	c.3584C>T	p.Thr1195Met	missense_variant	Exon 22 of 24		NP_570129.1	Q8WYK1
CNTNAP5	XM_017003316.2 link	c.3347C>T	p.Thr1116Met	missense_variant	Exon 21 of 23		XP_016858805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP5	ENST00000682447.1 link	c.3587C>T	p.Thr1196Met	missense_variant	Exon 22 of 24		NM_001367498.1	ENSP00000508115.1		A0A804HKY0
CNTNAP5	ENST00000431078.1 link	c.3584C>T	p.Thr1195Met	missense_variant	Exon 22 of 24	1		ENSP00000399013.1		Q8WYK1

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

GnomAD3 exomes

AF:

0.0154

AC:

3661

AN:

237804

Hom.:

AF XY:

0.0165

AC XY:

2122

AN XY:

128688

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 SAS exome

AF:

0.0156

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

Gnomad4 AFR exome

AF:

0.00434

Gnomad4 AMR exome

AF:

0.00981

Gnomad4 ASJ exome

AF:

0.0263

Gnomad4 EAS exome

AF:

0.0000509

Gnomad4 SAS exome

AF:

0.0164

Gnomad4 FIN exome

AF:

0.00501

Gnomad4 NFE exome

AF:

0.0235

Gnomad4 OTH exome

AF:

0.0192

GnomAD4 genome

AF:

0.0150

AC:

2287

AN:

152216

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

1003

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00611

Gnomad4 AMR

AF:

0.0116

Gnomad4 ASJ

AF:

0.0222

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0124

Gnomad4 FIN

AF:

0.00330

Gnomad4 NFE

AF:

0.0235

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0205

Hom.:

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

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CNTNAP5-related disorder

Benign:1

May 24, 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

0.074

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

3.8

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

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

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