2-124903032-C-T

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

2
16

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]

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
CNTNAP5NM_001367498.1 linkc.3587C>T p.Thr1196Met missense_variant Exon 22 of 24 ENST00000682447.1 NP_001354427.1
CNTNAP5NM_130773.4 linkc.3584C>T p.Thr1195Met missense_variant Exon 22 of 24 NP_570129.1 Q8WYK1
CNTNAP5XM_017003316.2 linkc.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
CNTNAP5ENST00000682447.1 linkc.3587C>T p.Thr1196Met missense_variant Exon 22 of 24 NM_001367498.1 ENSP00000508115.1 A0A804HKY0
CNTNAP5ENST00000431078.1 linkc.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.:
31
Cov.:
32
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.:
40
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.:
31
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.:
32
Cov.:
32
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.:
50
Bravo
AF:
0.0155
TwinsUK
AF:
0.0243
AC:
90
ALSPAC
AF:
0.0244
AC:
94
ESP6500AA
AF:
0.00518
AC:
22
ESP6500EA
AF:
0.0243
AC:
207
ExAC
AF:
0.0148
AC:
1790
Asia WGS
AF:
0.00375
AC:
13
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
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
3.8
DANN
Benign
0.95
DEOGEN2
Benign
0.074
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.029
N
LIST_S2
Benign
0.37
T
MetaRNN
Benign
0.0028
T
MetaSVM
Benign
-0.60
T
MutationAssessor
Uncertain
2.8
M
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.23
Sift
Benign
0.039
D
Sift4G
Uncertain
0.031
D
Polyphen
0.0050
B
Vest4
0.052
MPC
0.088
ClinPred
0.015
T
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.

Other links and lift over

dbSNP: rs34165507; hg19: chr2-125660609; COSMIC: COSV99081551; API