rs183440866
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1
The NM_001330078.2(NRXN1):c.4107G>A(p.Pro1369=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000861 in 1,613,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00036 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000057 ( 0 hom. )
Consequence
NRXN1
NM_001330078.2 synonymous
NM_001330078.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.85
Genes affected
NRXN1 (HGNC:8008): (neurexin 1) This gene encodes a single-pass type I membrane protein that belongs to the neurexin family. Neurexins are cell-surface receptors that bind neuroligins to form Ca(2+)-dependent neurexin/neuroligin complexes at synapses in the central nervous system. This complex is required for efficient neurotransmission and is involved in the formation of synaptic contacts. Three members of this gene family have been studied in detail and are estimated to generate over 3,000 variants through the use of two alternative promoters (alpha and beta) and extensive alternative splicing in each family member. Recently, a third promoter (gamma) was identified for this gene in the 3' region. Mutations in this gene are associated with Pitt-Hopkins-like syndrome-2 and may contribute to susceptibility to schizophrenia. [provided by RefSeq, Aug 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
?
Variant 2-50053292-C-T is Benign according to our data. Variant chr2-50053292-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 383233.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-50053292-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-1.85 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000361 (55/152224) while in subpopulation AFR AF= 0.00125 (52/41538). AF 95% confidence interval is 0.000981. There are 0 homozygotes in gnomad4. There are 23 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NRXN1 | NM_001330078.2 | c.4107G>A | p.Pro1369= | synonymous_variant | 21/23 | ENST00000401669.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NRXN1 | ENST00000401669.7 | c.4107G>A | p.Pro1369= | synonymous_variant | 21/23 | 5 | NM_001330078.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000362 AC: 55AN: 152106Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000916 AC: 23AN: 250962Hom.: 0 AF XY: 0.0000811 AC XY: 11AN XY: 135668
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GnomAD4 exome AF: 0.0000575 AC: 84AN: 1461676Hom.: 0 Cov.: 32 AF XY: 0.0000523 AC XY: 38AN XY: 727134
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GnomAD4 genome ? AF: 0.000361 AC: 55AN: 152224Hom.: 0 Cov.: 33 AF XY: 0.000309 AC XY: 23AN XY: 74424
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 11, 2021 | This variant is associated with the following publications: (PMID: 24429703) - |
Pitt-Hopkins-like syndrome 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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