rs2024513

chr2-50924881-A-Gchr2-50924881-A-T

Variant summary

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

The NM_001330078.2(NRXN1):c.790+1057T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 151,532 control chromosomes in the GnomAD database, including 10,572 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 0.34 (10572 hom., cov: 32)
• Consequence: NRXN1 NM_001330078.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.624

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRXN1	NM_001330078.2	c.790+1057T>C		intron_variant		ENST00000401669.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRXN1	ENST00000401669.7	c.790+1057T>C		intron_variant		5	NM_001330078.2	A1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 51862 AN: 151412 Hom.: 10578 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.342 AC: 51848 AN: 151532 Hom.: 10572 Cov.: 32 AF XY: 0.340 AC XY: 25200 AN XY: 74032

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.322

Alfa AF: 0.412 Hom.: 7367

Bravo AF: 0.316

Asia WGS AF: 0.221 AC: 767 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	5.8
Dann	Benign	0.33

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: rs2024513; hg19: chr2-51152019; COSMIC: COSV68020728;