rs1915174

Positions:

• chr2-50370777-G-A
• chr2-50370777-G-C
• chr2-50370777-G-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+94665C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 151,754 control chromosomes in the GnomAD database, including 26,550 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 0.57 (26550 hom., cov: 31)
• Consequence: NRXN1 NM_001330078.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRXN1	NM_001330078.2	c.3364+94665C>T		intron_variant		ENST00000401669.7	NP_001317007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRXN1	ENST00000401669.7	c.3364+94665C>T		intron_variant		5	NM_001330078.2	ENSP00000385017.2

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85778 AN: 151636 Hom.: 26498 Cov.: 31

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.566 AC: 85890 AN: 151754 Hom.: 26550 Cov.: 31 AF XY: 0.565 AC XY: 41926 AN XY: 74148

Gnomad4 AFR AF: 0.790

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.922

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.554

Alfa AF: 0.449 Hom.: 7553

Bravo AF: 0.592

Asia WGS AF: 0.721 AC: 2505 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.098
DANN	Benign	0.36

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: rs1915174; hg19: chr2-50597915;