rs2293847

Positions:

• chr14-79860739-T-C
• chr14-79860739-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330195.2(NRXN3):​c.4094-603T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,134 control chromosomes in the GnomAD database, including 11,622 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 0.37 (11622 hom., cov: 33)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.375

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRXN3	NM_001330195.2	c.4094-603T>C		intron_variant		ENST00000335750.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRXN3	ENST00000335750.7	c.4094-603T>C		intron_variant		5	NM_001330195.2	P1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56965 AN: 152016 Hom.: 11595 Cov.: 33

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.375 AC: 57026 AN: 152134 Hom.: 11622 Cov.: 33 AF XY: 0.376 AC XY: 27998 AN XY: 74382

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.375

Alfa AF: 0.412 Hom.: 27247

Bravo AF: 0.376

Asia WGS AF: 0.375 AC: 1304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.81
DANN	Benign	0.74

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

Other links and lift over

dbSNP: rs2293847; hg19: chr14-80327082;