2-50041478-T-C

Position:

• chr2-50041478-T-C

Variant summary

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

The NM_001330078.2(NRXN1):​c.4128+11793A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,160 control chromosomes in the GnomAD database, including 3,726 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 0.19 (3726 hom., cov: 32)
• Consequence: NRXN1 NM_001330078.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.794

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRXN1	NM_001330078.2	c.4128+11793A>G		intron_variant		ENST00000401669.7	NP_001317007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRXN1	ENST00000401669.7	c.4128+11793A>G		intron_variant		5	NM_001330078.2	ENSP00000385017.2

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29143 AN: 152042 Hom.: 3727 Cov.: 32

Gnomad AFR AF: 0.0494

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.0630

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.191 AC: 29127 AN: 152160 Hom.: 3726 Cov.: 32 AF XY: 0.190 AC XY: 14129 AN XY: 74370

Gnomad4 AFR AF: 0.0493

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.0630

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.182

Alfa AF: 0.246 Hom.: 3146

Bravo AF: 0.170

Asia WGS AF: 0.118 AC: 409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.7
DANN	Benign	0.73

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: rs17495366; hg19: chr2-50268616;