rs8020920

Variant names:

• chr14-78760533-G-A
• rs8020920
• NM_001330195.2:c.2045-43087G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-78760533-G-A
• chr14-78760533-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.2045-43087G>A 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 147,062 control chromosomes in the GnomAD database, including 10,376 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 0.31 (10376 hom., cov: 25)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.458
• Publications: 2 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

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 (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.2045-43087G>A		intron_variant	Intron 8 of 20	ENST00000335750.7	NP_001317124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.2045-43087G>A		intron_variant	Intron 8 of 20	5	NM_001330195.2	ENSP00000338349.7

Frequencies

GnomAD3 genomes AF: 0.307 AC: 45112 AN: 146944 Hom.: 10337 Cov.: 25

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.0926

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.307 AC: 45204 AN: 147062 Hom.: 10376 Cov.: 25 AF XY: 0.306 AC XY: 21832 AN XY: 71410

African (AFR) AF: 0.656 AC: 25732 AN: 39242

American (AMR) AF: 0.174 AC: 2519 AN: 14494

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 655 AN: 3428

East Asian (EAS) AF: 0.230 AC: 1147 AN: 4992

South Asian (SAS) AF: 0.317 AC: 1405 AN: 4438

European-Finnish (FIN) AF: 0.190 AC: 1908 AN: 10026

Middle Eastern (MID) AF: 0.236 AC: 68 AN: 288

European-Non Finnish (NFE) AF: 0.165 AC: 11126 AN: 67242

Other (OTH) AF: 0.278 AC: 561 AN: 2016

Alfa AF: 0.206 Hom.: 14567

Bravo AF: 0.322

Asia WGS AF: 0.337 AC: 1173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.3
DANN	Benign	0.62
PhyloP100		0.46
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: rs8020920; hg19: chr14-79226876;