rs2293839

Variant names:

• chr14-79851117-G-A
• rs2293839
• NM_001330195.2:c.4094-10225G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-79851117-G-A
• chr14-79851117-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330195.2(NRXN3):​c.4094-10225G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,910 control chromosomes in the GnomAD database, including 14,475 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 0.43 (14475 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290
• Publications: 4 publications found

Genes affected

NRXN3 (HGNC:8010): (neurexin 3) This gene encodes a member of a family of proteins that function in the nervous system as receptors and cell adhesion molecules. Extensive alternative splicing and the use of alternative promoters results in multiple transcript variants and protein isoforms for this gene, but the full-length nature of many of these variants has not been determined. Transcripts that initiate from an upstream promoter encode alpha isoforms, which contain epidermal growth factor-like (EGF-like) sequences and laminin G domains. Transcripts initiating from the downstream promoter encode beta isoforms, which lack EGF-like sequences. Genetic variation at this locus has been associated with a range of behavioral phenotypes, including alcohol dependence and autism spectrum disorder. [provided by RefSeq, Dec 2012]

NRXN3 Gene-Disease associations (from GenCC):

• autism

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ENSG00000258416 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.4094-10225G>A		intron_variant	Intron 20 of 20	ENST00000335750.7	NP_001317124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.4094-10225G>A		intron_variant	Intron 20 of 20	5	NM_001330195.2	ENSP00000338349.7

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64814 AN: 151792 Hom.: 14438 Cov.: 32

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.427 AC: 64901 AN: 151910 Hom.: 14475 Cov.: 32 AF XY: 0.425 AC XY: 31570 AN XY: 74248

African (AFR) AF: 0.543 AC: 22525 AN: 41460

American (AMR) AF: 0.342 AC: 5224 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1044 AN: 3470

East Asian (EAS) AF: 0.562 AC: 2891 AN: 5148

South Asian (SAS) AF: 0.509 AC: 2450 AN: 4810

European-Finnish (FIN) AF: 0.355 AC: 3742 AN: 10534

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.379 AC: 25755 AN: 67918

Other (OTH) AF: 0.398 AC: 838 AN: 2104

Alfa AF: 0.423 Hom.: 5604

Bravo AF: 0.429

Asia WGS AF: 0.503 AC: 1745 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.4
DANN	Benign	0.71
PhyloP100		-0.029
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2293839; hg19: chr14-80317460;