rs73471053
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_014141.6(CNTNAP2):c.1119G>A(p.Thr373=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,613,554 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0089 ( 17 hom., cov: 32)
Exomes 𝑓: 0.00095 ( 23 hom. )
Consequence
CNTNAP2
NM_014141.6 synonymous
NM_014141.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.38
Genes affected
CNTNAP2 (HGNC:13830): (contactin associated protein 2) This gene encodes a member of the neurexin family which functions 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, thrombospondin N-terminal-like domains and a putative PDZ binding site. This protein is localized at the juxtaparanodes of myelinated axons, and mediates interactions between neurons and glia during nervous system development and is also involved in localization of potassium channels within differentiating axons. This gene encompasses almost 1.5% of chromosome 7 and is one of the largest genes in the human genome. It is directly bound and regulated by forkhead box protein P2, a transcription factor related to speech and language development. This gene has been implicated in multiple neurodevelopmental disorders, including Gilles de la Tourette syndrome, schizophrenia, epilepsy, autism, ADHD and intellectual disability. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 7-147132280-G-A is Benign according to our data. Variant chr7-147132280-G-A is described in ClinVar as [Benign]. Clinvar id is 128799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-147132280-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-1.38 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00894 (1359/152056) while in subpopulation AFR AF= 0.0316 (1309/41462). AF 95% confidence interval is 0.0301. There are 17 homozygotes in gnomad4. There are 632 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 17 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CNTNAP2 | NM_014141.6 | c.1119G>A | p.Thr373= | synonymous_variant | 8/24 | ENST00000361727.8 | NP_054860.1 | |
CNTNAP2 | XM_017011950.3 | c.1119G>A | p.Thr373= | synonymous_variant | 8/14 | XP_016867439.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CNTNAP2 | ENST00000361727.8 | c.1119G>A | p.Thr373= | synonymous_variant | 8/24 | 1 | NM_014141.6 | ENSP00000354778 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00894 AC: 1358AN: 151938Hom.: 17 Cov.: 32
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GnomAD3 exomes AF: 0.00229 AC: 575AN: 251280Hom.: 9 AF XY: 0.00151 AC XY: 205AN XY: 135808
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GnomAD4 exome AF: 0.000949 AC: 1387AN: 1461498Hom.: 23 Cov.: 32 AF XY: 0.000855 AC XY: 622AN XY: 727062
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GnomAD4 genome AF: 0.00894 AC: 1359AN: 152056Hom.: 17 Cov.: 32 AF XY: 0.00850 AC XY: 632AN XY: 74326
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 04, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 03, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Cortical dysplasia-focal epilepsy syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 09, 2016 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at