rs4563262

chr2-50459235-T-Cchr2-50459235-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.3364+6207A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,084 control chromosomes in the GnomAD database, including 6,983 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 0.23 (6983 hom., cov: 32)
• Consequence: NRXN1 NM_001330078.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRXN1	NM_001330078.2	c.3364+6207A>G		intron_variant		ENST00000401669.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRXN1	ENST00000401669.7	c.3364+6207A>G		intron_variant		5	NM_001330078.2	A1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34344 AN: 151964 Hom.: 6979 Cov.: 32

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.0930

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.0520

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0701

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.226 AC: 34394 AN: 152084 Hom.: 6983 Cov.: 32 AF XY: 0.224 AC XY: 16681 AN XY: 74352

Gnomad4 AFR AF: 0.512

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.0930

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.0520

Gnomad4 NFE AF: 0.0701

Gnomad4 OTH AF: 0.198

Alfa AF: 0.122 Hom.: 1147

Bravo AF: 0.257

Asia WGS AF: 0.357 AC: 1241 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	9.7
Dann	Benign	0.86

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: rs4563262; hg19: chr2-50686373;