rs10490242

chr2-50088357-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.3718+2966G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,958 control chromosomes in the GnomAD database, including 8,231 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 0.32 (8231 hom., cov: 32)
• Consequence: NRXN1 NM_001330078.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640

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=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRXN1	NM_001330078.2	c.3718+2966G>A		intron_variant		ENST00000401669.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRXN1	ENST00000401669.7	c.3718+2966G>A		intron_variant		5	NM_001330078.2	A1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48734 AN: 151840 Hom.: 8235 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.321 AC: 48736 AN: 151958 Hom.: 8231 Cov.: 32 AF XY: 0.316 AC XY: 23492 AN XY: 74282

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.310

Alfa AF: 0.361 Hom.: 1270

Bravo AF: 0.304

Asia WGS AF: 0.278 AC: 966 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	5.7
Dann	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10490242; hg19: chr2-50315495; COSMIC: COSV60519728;