rs10495995

Positions:

• chr2-50021775-A-G
• chr2-50021775-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.4128+31496T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 152,076 control chromosomes in the GnomAD database, including 39,912 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 0.72 (39912 hom., cov: 32)
• Consequence: NRXN1 NM_001330078.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRXN1	NM_001330078.2	c.4128+31496T>C		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+31496T>C		intron_variant		5	NM_001330078.2	ENSP00000385017	A1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109778 AN: 151958 Hom.: 39871 Cov.: 32

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.702

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

GnomAD4 genome AF: 0.722 AC: 109863 AN: 152076 Hom.: 39912 Cov.: 32 AF XY: 0.721 AC XY: 53574 AN XY: 74336

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.672

Gnomad4 ASJ AF: 0.680

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.748

Gnomad4 NFE AF: 0.708

Gnomad4 OTH AF: 0.697

Alfa AF: 0.729 Hom.: 5033

Bravo AF: 0.717

Asia WGS AF: 0.633 AC: 2201 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.57

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: rs10495995; hg19: chr2-50248913;