rs10187911

Variant names:

• chr2-50420809-C-A
• rs10187911
• NM_001330078.2:c.3364+44633G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-50420809-C-A
• chr2-50420809-C-G
• chr2-50420809-C-T

Variant summary

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

The NM_001330078.2(NRXN1):​c.3364+44633G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 151,742 control chromosomes in the GnomAD database, including 1,863 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 0.13 (1863 hom., cov: 31)
• Consequence: NRXN1 NM_001330078.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• Publications: 5 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)

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 = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN1	NM_001330078.2	c.3364+44633G>T		intron_variant	Intron 17 of 22	ENST00000401669.7	NP_001317007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN1	ENST00000401669.7	c.3364+44633G>T		intron_variant	Intron 17 of 22	5	NM_001330078.2	ENSP00000385017.2

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19077 AN: 151624 Hom.: 1864 Cov.: 31

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.0707

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.0355

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0580

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.126 AC: 19098 AN: 151742 Hom.: 1863 Cov.: 31 AF XY: 0.128 AC XY: 9455 AN XY: 74150

African (AFR) AF: 0.213 AC: 8806 AN: 41368

American (AMR) AF: 0.169 AC: 2576 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.0707 AC: 245 AN: 3466

East Asian (EAS) AF: 0.414 AC: 2128 AN: 5136

South Asian (SAS) AF: 0.156 AC: 748 AN: 4806

European-Finnish (FIN) AF: 0.0355 AC: 375 AN: 10554

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0580 AC: 3937 AN: 67882

Other (OTH) AF: 0.118 AC: 249 AN: 2104

Alfa AF: 0.0621 Hom.: 172

Bravo AF: 0.145

Asia WGS AF: 0.248 AC: 860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.043
DANN	Benign	0.52
PhyloP100		-2.0
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: rs10187911; hg19: chr2-50647947;