chr2-50649904-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001330078.2(NRXN1):​c.833-26289G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 151,890 control chromosomes in the GnomAD database, including 1,049 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 1049 hom., cov: 32)

Consequence

NRXN1
NM_001330078.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00500

Publications

1 publications found
Variant links:
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]
NRXN1 Gene-Disease associations (from GenCC):
  • complex neurodevelopmental disorder
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • chromosome 2p16.3 deletion syndrome
    Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • Pitt-Hopkins-like syndrome 2
    Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • autism
    Inheritance: AD Classification: MODERATE Submitted by: G2P
  • schizophrenia
    Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NRXN1NM_001330078.2 linkc.833-26289G>A intron_variant Intron 5 of 22 ENST00000401669.7 NP_001317007.1 E7ERL8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NRXN1ENST00000401669.7 linkc.833-26289G>A intron_variant Intron 5 of 22 5 NM_001330078.2 ENSP00000385017.2 E7ERL8

Frequencies

GnomAD3 genomes
AF:
0.112
AC:
16937
AN:
151770
Hom.:
1051
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0733
Gnomad AMI
AF:
0.180
Gnomad AMR
AF:
0.109
Gnomad ASJ
AF:
0.134
Gnomad EAS
AF:
0.0705
Gnomad SAS
AF:
0.0909
Gnomad FIN
AF:
0.101
Gnomad MID
AF:
0.201
Gnomad NFE
AF:
0.139
Gnomad OTH
AF:
0.136
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.111
AC:
16927
AN:
151890
Hom.:
1049
Cov.:
32
AF XY:
0.109
AC XY:
8127
AN XY:
74242
show subpopulations
African (AFR)
AF:
0.0731
AC:
3033
AN:
41466
American (AMR)
AF:
0.108
AC:
1648
AN:
15214
Ashkenazi Jewish (ASJ)
AF:
0.134
AC:
464
AN:
3470
East Asian (EAS)
AF:
0.0706
AC:
362
AN:
5126
South Asian (SAS)
AF:
0.0907
AC:
437
AN:
4816
European-Finnish (FIN)
AF:
0.101
AC:
1068
AN:
10594
Middle Eastern (MID)
AF:
0.192
AC:
56
AN:
292
European-Non Finnish (NFE)
AF:
0.139
AC:
9415
AN:
67886
Other (OTH)
AF:
0.132
AC:
280
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
774
1548
2321
3095
3869
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
192
384
576
768
960
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.132
Hom.:
1051
Bravo
AF:
0.110
Asia WGS
AF:
0.0600
AC:
210
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
3.6
DANN
Benign
0.69
PhyloP100
0.0050
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs858953; hg19: chr2-50877042; API