rs7157915

chr14-78567834-A-C

Variant summary

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

The NM_001330195.2(NRXN3):c.758-77286A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0611 in 152,120 control chromosomes in the GnomAD database, including 421 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 0.061 (421 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRXN3	NM_001330195.2	c.758-77286A>C		intron_variant		ENST00000335750.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRXN3	ENST00000335750.7	c.758-77286A>C		intron_variant		5	NM_001330195.2	P1

Frequencies

GnomAD3 genomes AF: 0.0609 AC: 9257 AN: 152002 Hom.: 412 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0397

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.0694

Gnomad FIN AF: 0.00829

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0311

Gnomad OTH AF: 0.0455

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

GnomAD4 genome AF: 0.0611 AC: 9288 AN: 152120 Hom.: 421 Cov.: 32 AF XY: 0.0598 AC XY: 4450 AN XY: 74364

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.0396

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.0703

Gnomad4 FIN AF: 0.00829

Gnomad4 NFE AF: 0.0311

Gnomad4 OTH AF: 0.0450

Alfa AF: 0.0444 Hom.: 45

Bravo AF: 0.0667

Asia WGS AF: 0.108 AC: 375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.033
Dann	Benign	0.60

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: rs7157915; hg19: chr14-79034177;