rs11681755

Variant names:

• chr2-50230505-A-G
• rs11681755
• NM_001330078.2:c.3546+6284T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-50230505-A-G
• chr2-50230505-A-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.3546+6284T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0943 in 152,110 control chromosomes in the GnomAD database, including 826 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 0.094 (826 hom., cov: 32)
• Consequence: NRXN1 NM_001330078.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN1	NM_001330078.2	c.3546+6284T>C		intron_variant	Intron 18 of 22	ENST00000401669.7	NP_001317007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN1	ENST00000401669.7	c.3546+6284T>C		intron_variant	Intron 18 of 22	5	NM_001330078.2	ENSP00000385017.2

Frequencies

GnomAD3 genomes AF: 0.0943 AC: 14335 AN: 151992 Hom.: 824 Cov.: 32

Gnomad AFR AF: 0.0501

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0756

Gnomad ASJ AF: 0.0813

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0957

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

GnomAD4 genome AF: 0.0943 AC: 14340 AN: 152110 Hom.: 826 Cov.: 32 AF XY: 0.0970 AC XY: 7214 AN XY: 74340

African (AFR) AF: 0.0501 AC: 2081 AN: 41548

American (AMR) AF: 0.0755 AC: 1151 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.0813 AC: 282 AN: 3468

East Asian (EAS) AF: 0.135 AC: 693 AN: 5136

South Asian (SAS) AF: 0.141 AC: 681 AN: 4828

European-Finnish (FIN) AF: 0.153 AC: 1620 AN: 10600

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.111 AC: 7539 AN: 67982

Other (OTH) AF: 0.0980 AC: 206 AN: 2102

Alfa AF: 0.101 Hom.: 145

Bravo AF: 0.0837

Asia WGS AF: 0.120 AC: 415 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.2
DANN	Benign	0.43
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

Other links and lift over

dbSNP: rs11681755; hg19: chr2-50457643;