rs2123388

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001330078.2(NRXN1):​c.3718+5177C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 151,984 control chromosomes in the GnomAD database, including 5,673 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 0.26 ( 5673 hom., cov: 32)

Consequence

NRXN1
NM_001330078.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.585
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NRXN1NM_001330078.2 linkuse as main transcriptc.3718+5177C>A intron_variant ENST00000401669.7 NP_001317007.1 E7ERL8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NRXN1ENST00000401669.7 linkuse as main transcriptc.3718+5177C>A intron_variant 5 NM_001330078.2 ENSP00000385017.2 E7ERL8

Frequencies

GnomAD3 genomes
AF:
0.264
AC:
40058
AN:
151866
Hom.:
5658
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.269
Gnomad AMI
AF:
0.458
Gnomad AMR
AF:
0.386
Gnomad ASJ
AF:
0.311
Gnomad EAS
AF:
0.362
Gnomad SAS
AF:
0.276
Gnomad FIN
AF:
0.146
Gnomad MID
AF:
0.326
Gnomad NFE
AF:
0.237
Gnomad OTH
AF:
0.278
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.264
AC:
40112
AN:
151984
Hom.:
5673
Cov.:
32
AF XY:
0.264
AC XY:
19585
AN XY:
74286
show subpopulations
Gnomad4 AFR
AF:
0.269
Gnomad4 AMR
AF:
0.387
Gnomad4 ASJ
AF:
0.311
Gnomad4 EAS
AF:
0.361
Gnomad4 SAS
AF:
0.275
Gnomad4 FIN
AF:
0.146
Gnomad4 NFE
AF:
0.237
Gnomad4 OTH
AF:
0.278
Alfa
AF:
0.234
Hom.:
570
Bravo
AF:
0.289
Asia WGS
AF:
0.271
AC:
945
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.67
DANN
Benign
0.36

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: rs2123388; hg19: chr2-50313284; API