rs11125321

Variant names:

• chr2-50624879-G-A
• rs11125321
• NM_001330078.2:c.833-1264C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-50624879-G-A
• chr2-50624879-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330078.2(NRXN1):​c.833-1264C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 151,792 control chromosomes in the GnomAD database, including 26,444 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 0.59 (26439 hom., cov: 31)
  • Exomes 𝑓: 0.67 (5 hom.)
• Consequence: NRXN1 NM_001330078.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• Publications: 2 publications found

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)

ENSG00000283058 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN1	NM_001330078.2	c.833-1264C>T		intron_variant	Intron 5 of 22	ENST00000401669.7	NP_001317007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN1	ENST00000401669.7	c.833-1264C>T		intron_variant	Intron 5 of 22	5	NM_001330078.2	ENSP00000385017.2

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89188 AN: 151650 Hom.: 26421 Cov.: 31

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.583

GnomAD4 exome AF: 0.667 AC: 16 AN: 24 Hom.: 5 Cov.: 0 AF XY: 0.643 AC XY: 9 AN XY: 14

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.700 AC: 14 AN: 20

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.588 AC: 89257 AN: 151768 Hom.: 26439 Cov.: 31 AF XY: 0.590 AC XY: 43764 AN XY: 74156

African (AFR) AF: 0.585 AC: 24207 AN: 41380

American (AMR) AF: 0.605 AC: 9212 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2024 AN: 3468

East Asian (EAS) AF: 0.737 AC: 3784 AN: 5134

South Asian (SAS) AF: 0.650 AC: 3120 AN: 4802

European-Finnish (FIN) AF: 0.561 AC: 5928 AN: 10564

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39161 AN: 67878

Other (OTH) AF: 0.583 AC: 1230 AN: 2108

Alfa AF: 0.586 Hom.: 13370

Bravo AF: 0.591

Asia WGS AF: 0.708 AC: 2460 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.90
DANN	Benign	0.70
PhyloP100		-0.12
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

Other links and lift over

dbSNP: rs11125321; hg19: chr2-50852017;