rs930295

Variant names:

• chr2-50006214-A-C
• rs930295
• NM_001330078.2:c.4128+47057T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-50006214-A-C
• chr2-50006214-A-G
• chr2-50006214-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.4128+47057T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 152,104 control chromosomes in the GnomAD database, including 59,655 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 0.88 (59655 hom., cov: 32)
• Consequence: NRXN1 NM_001330078.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 11 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN1	NM_001330078.2	c.4128+47057T>G		intron_variant	Intron 21 of 22	ENST00000401669.7	NP_001317007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN1	ENST00000401669.7	c.4128+47057T>G		intron_variant	Intron 21 of 22	5	NM_001330078.2	ENSP00000385017.2

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134257 AN: 151986 Hom.: 59601 Cov.: 32

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.896

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.797

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.873

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

GnomAD4 genome AF: 0.883 AC: 134365 AN: 152104 Hom.: 59655 Cov.: 32 AF XY: 0.882 AC XY: 65613 AN XY: 74352

African (AFR) AF: 0.968 AC: 40203 AN: 41534

American (AMR) AF: 0.896 AC: 13678 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.862 AC: 2993 AN: 3472

East Asian (EAS) AF: 0.797 AC: 4094 AN: 5134

South Asian (SAS) AF: 0.833 AC: 4011 AN: 4814

European-Finnish (FIN) AF: 0.874 AC: 9254 AN: 10590

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.841 AC: 57172 AN: 67976

Other (OTH) AF: 0.867 AC: 1835 AN: 2116

Alfa AF: 0.858 Hom.: 69642

Bravo AF: 0.890

Asia WGS AF: 0.779 AC: 2711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.31
PhyloP100		-1.5
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: rs930295; hg19: chr2-50233352;