rs10490227

chr2-50432377-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330078.2(NRXN1):c.3364+33065G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,172 control chromosomes in the GnomAD database, including 2,817 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 0.17 (2817 hom., cov: 32)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: NRXN1 NM_001330078.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRXN1	NM_001330078.2	c.3364+33065G>A		intron_variant		ENST00000401669.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRXN1	ENST00000401669.7	c.3364+33065G>A		intron_variant		5	NM_001330078.2	A1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25554 AN: 152044 Hom.: 2815 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.100 AC: 1 AN: 10 Hom.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.168 AC: 25571 AN: 152162 Hom.: 2817 Cov.: 32 AF XY: 0.171 AC XY: 12716 AN XY: 74398

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.169

Alfa AF: 0.125 Hom.: 3081

Bravo AF: 0.185

Asia WGS AF: 0.340 AC: 1185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.9
Dann	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs10490227; hg19: chr2-50659515;