2-50336767-T-G

Position:

• chr2-50336767-T-G

Variant summary

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

The NM_001330078.2(NRXN1):​c.3365-99797A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,046 control chromosomes in the GnomAD database, including 13,570 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 0.37 (13570 hom., cov: 32)
• Consequence: NRXN1 NM_001330078.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.970

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRXN1	NM_001330078.2	c.3365-99797A>C		intron_variant		ENST00000401669.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRXN1	ENST00000401669.7	c.3365-99797A>C		intron_variant		5	NM_001330078.2	A1
	ENST00000649515.1	n.243+686T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55628 AN: 151928 Hom.: 13526 Cov.: 32

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.367 AC: 55736 AN: 152046 Hom.: 13570 Cov.: 32 AF XY: 0.363 AC XY: 26997 AN XY: 74332

Gnomad4 AFR AF: 0.685

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.340

Alfa AF: 0.244 Hom.: 10319

Bravo AF: 0.399

Asia WGS AF: 0.422 AC: 1470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.70

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: rs9309181; hg19: chr2-50563905;