rs11889082

Variant names:

• chr2-51044980-A-G
• rs11889082
• ENST00000440698.1:n.417-7377A>G

Variant summary

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

The ENST00000440698.1(NRXN1-DT):​n.417-7377A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0999 in 152,256 control chromosomes in the GnomAD database, including 851 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 0.10 (851 hom., cov: 33)
• Consequence: NRXN1-DT ENST00000440698.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180
• Publications: 1 publications found

Genes affected

NRXN1-DT (HGNC:52686): (NRXN1 divergent transcript)

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)

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 (SAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000440698.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN1-DT	NR_135237.1		n.417-7377A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN1-DT	ENST00000440698.1	TSL:2	n.417-7377A>G		intron	N/A
	NRXN1	ENST00000635126.1	TSL:5	n.320-11846T>C		intron	N/A
	NRXN1	ENST00000635310.1	TSL:5	n.426-15786T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0998 AC: 15181 AN: 152138 Hom.: 846 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0715

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.0733

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0845

Gnomad OTH AF: 0.114

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0999 AC: 15207 AN: 152256 Hom.: 851 Cov.: 33 AF XY: 0.101 AC XY: 7496 AN XY: 74444

African (AFR) AF: 0.127 AC: 5282 AN: 41548

American (AMR) AF: 0.0714 AC: 1093 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 461 AN: 3470

East Asian (EAS) AF: 0.121 AC: 628 AN: 5178

South Asian (SAS) AF: 0.174 AC: 842 AN: 4832

European-Finnish (FIN) AF: 0.0733 AC: 778 AN: 10610

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0846 AC: 5750 AN: 67992

Other (OTH) AF: 0.118 AC: 250 AN: 2112

Alfa AF: 0.0903 Hom.: 123

Bravo AF: 0.0998

Asia WGS AF: 0.163 AC: 565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.64
PhyloP100		0.018

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11889082; hg19: chr2-51272118;