Variant 2-50465422-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001330078.2(NRXN1):c.3364+20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,594,926 control chromosomes in the GnomAD database, including 78,421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6000 hom., cov: 31)

Exomes 𝑓: 0.31 ( 72421 hom. )

Consequence

NRXN1
NM_001330078.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.110

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 2-50465422-A-G is Benign according to our data. Variant chr2-50465422-A-G is described in ClinVar as [Benign]. Clinvar id is 93601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-50465422-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRXN1	NM_001330078.2 linkuse as main transcript	c.3364+20T>C		intron_variant		ENST00000401669.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRXN1	ENST00000401669.7 linkuse as main transcript	c.3364+20T>C		intron_variant		5	NM_001330078.2	A1

Frequencies

GnomAD3 genomes

AF:

0.267

AC:

40426

AN:

151610

Hom.:

5991

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.343

Gnomad ASJ

AF:

0.220

Gnomad EAS

AF:

0.430

Gnomad SAS

AF:

0.481

Gnomad FIN

AF:

0.239

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.272

GnomAD3 exomes

AF:

0.324

AC:

74025

AN:

228348

Hom.:

12895

AF XY:

0.327

AC XY:

40284

AN XY:

123100

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.404

Gnomad ASJ exome

AF:

0.219

Gnomad EAS exome

AF:

0.446

Gnomad SAS exome

AF:

0.464

Gnomad FIN exome

AF:

0.249

Gnomad NFE exome

AF:

0.291

Gnomad OTH exome

AF:

0.287

GnomAD4 exome

AF:

0.311

AC:

449181

AN:

1443200

Hom.:

72421

Cov.:

AF XY:

0.315

AC XY:

225462

AN XY:

716454

show subpopulations

Gnomad4 AFR exome

AF:

0.151

Gnomad4 AMR exome

AF:

0.402

Gnomad4 ASJ exome

AF:

0.219

Gnomad4 EAS exome

AF:

0.394

Gnomad4 SAS exome

AF:

0.464

Gnomad4 FIN exome

AF:

0.256

Gnomad4 NFE exome

AF:

0.304

Gnomad4 OTH exome

AF:

0.301

GnomAD4 genome

AF:

0.267

AC:

40470

AN:

151726

Hom.:

6000

Cov.:

AF XY:

0.272

AC XY:

20180

AN XY:

74140

show subpopulations

Gnomad4 AFR

AF:

0.160

Gnomad4 AMR

AF:

0.344

Gnomad4 ASJ

AF:

0.220

Gnomad4 EAS

AF:

0.430

Gnomad4 SAS

AF:

0.481

Gnomad4 FIN

AF:

0.239

Gnomad4 NFE

AF:

0.295

Gnomad4 OTH

AF:

0.274

Alfa

AF:

0.282

Hom.:

9471

Bravo

AF:

0.267

Asia WGS

AF:

0.439

AC:

1525

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 02, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Pitt-Hopkins-like syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

Cadd

Benign

0.078

Dann

Benign

0.28

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over