Variant chr2-50506820-T-C 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.2375-203A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 542,316 control chromosomes in the GnomAD database, including 38,971 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9911 hom., cov: 30)

Exomes 𝑓: 0.37 ( 29060 hom. )

Consequence

NRXN1
NM_001330078.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0910

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=-0.59).

BP6

Variant 2-50506820-T-C is Benign according to our data. Variant chr2-50506820-T-C is described in ClinVar as [Benign]. Clinvar id is 667703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.398 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.2375-203A>G		intron_variant		ENST00000401669.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRXN1	ENST00000401669.7 linkuse as main transcript	c.2375-203A>G		intron_variant		5	NM_001330078.2	A1

Frequencies

GnomAD3 genomes

AF:

0.348

AC:

52832

AN:

151706

Hom.:

9916

Cov.:

show subpopulations

Gnomad AFR

AF:

0.268

Gnomad AMI

AF:

0.467

Gnomad AMR

AF:

0.284

Gnomad ASJ

AF:

0.476

Gnomad EAS

AF:

0.0947

Gnomad SAS

AF:

0.388

Gnomad FIN

AF:

0.458

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.402

Gnomad OTH

AF:

0.358

GnomAD4 exome

AF:

0.370

AC:

144578

AN:

390492

Hom.:

29060

Cov.:

AF XY:

0.373

AC XY:

75725

AN XY:

202916

show subpopulations

Gnomad4 AFR exome

AF:

0.271

Gnomad4 AMR exome

AF:

0.238

Gnomad4 ASJ exome

AF:

0.467

Gnomad4 EAS exome

AF:

0.0794

Gnomad4 SAS exome

AF:

0.395

Gnomad4 FIN exome

AF:

0.439

Gnomad4 NFE exome

AF:

0.403

Gnomad4 OTH exome

AF:

0.372

GnomAD4 genome

AF:

0.348

AC:

52830

AN:

151824

Hom.:

9911

Cov.:

AF XY:

0.348

AC XY:

25810

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.267

Gnomad4 AMR

AF:

0.284

Gnomad4 ASJ

AF:

0.476

Gnomad4 EAS

AF:

0.0941

Gnomad4 SAS

AF:

0.388

Gnomad4 FIN

AF:

0.458

Gnomad4 NFE

AF:

0.402

Gnomad4 OTH

AF:

0.355

Alfa

AF:

0.370

Hom.:

1731

Bravo

AF:

0.324

Asia WGS

AF:

0.253

AC:

880

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

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

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