2-124524333-C-T
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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
NM_001367498.1 missense
Scores
1
7
10
Clinical Significance
Conservation
PhyloP100: 1.85
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]
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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 | UniProt |
---|---|---|---|---|---|---|---|
CNTNAP5 | NM_001367498.1 | c.1358C>T | p.Ser453Leu | missense_variant | 9/24 | ENST00000682447.1 | |
CNTNAP5 | NM_130773.4 | c.1355C>T | p.Ser452Leu | missense_variant | 9/24 | ||
CNTNAP5 | XM_017003316.2 | c.1358C>T | p.Ser453Leu | missense_variant | 9/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNTNAP5 | ENST00000682447.1 | c.1358C>T | p.Ser453Leu | missense_variant | 9/24 | NM_001367498.1 | A1 | ||
CNTNAP5 | ENST00000431078.1 | c.1355C>T | p.Ser452Leu | missense_variant | 9/24 | 1 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0342 AC: 5206AN: 152058Hom.: 130 Cov.: 32
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GnomAD3 exomes AF: 0.0360 AC: 8958AN: 248590Hom.: 250 AF XY: 0.0364 AC XY: 4910AN XY: 134826
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GnomAD4 exome AF: 0.0415 AC: 60635AN: 1461470Hom.: 1424 Cov.: 31 AF XY: 0.0413 AC XY: 30058AN XY: 727016
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GnomAD4 genome AF: 0.0342 AC: 5201AN: 152174Hom.: 130 Cov.: 32 AF XY: 0.0365 AC XY: 2715AN XY: 74392
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
CNTNAP5-related disorder Benign:1
Benign, no assertion criteria provided | 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Benign
D
Sift4G
Uncertain
T
Polyphen
B
Vest4
MPC
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at