rs2067730

Variant names:

• chr14-79847994-T-G
• rs2067730
• NM_001330195.2:c.4094-13348T>G

Variant summary

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

The NM_001330195.2(NRXN3):​c.4094-13348T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,076 control chromosomes in the GnomAD database, including 1,902 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 0.15 (1902 hom., cov: 31)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.4094-13348T>G		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.4094-13348T>G		intron_variant	Intron 20 of 20	5	NM_001330195.2	ENSP00000338349.7

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22771 AN: 151958 Hom.: 1906 Cov.: 31

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.0497

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0855

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.150 AC: 22776 AN: 152076 Hom.: 1902 Cov.: 31 AF XY: 0.147 AC XY: 10931 AN XY: 74362

African (AFR) AF: 0.202 AC: 8389 AN: 41452

American (AMR) AF: 0.113 AC: 1726 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 714 AN: 3466

East Asian (EAS) AF: 0.0499 AC: 258 AN: 5174

South Asian (SAS) AF: 0.115 AC: 553 AN: 4814

European-Finnish (FIN) AF: 0.0855 AC: 906 AN: 10596

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9649 AN: 67988

Other (OTH) AF: 0.149 AC: 314 AN: 2110

Alfa AF: 0.142 Hom.: 264

Bravo AF: 0.154

Asia WGS AF: 0.0700 AC: 245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.2
DANN	Benign	0.73
PhyloP100		1.2
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: rs2067730; hg19: chr14-80314337;