chr2-50291196-G-A

Position:

• chr2-50291196-G-A

Variant summary

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

The NM_001330078.2(NRXN1):​c.3365-54226C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 150,600 control chromosomes in the GnomAD database, including 4,274 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 0.22 (4274 hom., cov: 31)
• Consequence: NRXN1 NM_001330078.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRXN1	NM_001330078.2	c.3365-54226C>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.3365-54226C>T		intron_variant		5	NM_001330078.2	ENSP00000385017	A1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33498 AN: 150550 Hom.: 4274 Cov.: 31

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.223 AC: 33520 AN: 150600 Hom.: 4274 Cov.: 31 AF XY: 0.225 AC XY: 16501 AN XY: 73394

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.363

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.241

Alfa AF: 0.105 Hom.: 197

Bravo AF: 0.225

Asia WGS AF: 0.302 AC: 1051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.5
DANN	Benign	0.40

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: rs1113099; hg19: chr2-50518334;