rs504915

Variant names:

• chr11-64696613-T-A
• rs504915
• NM_015080.4:c.748+1162A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-64696613-T-A
• chr11-64696613-T-C

Variant summary

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

The NM_015080.4(NRXN2):​c.748+1162A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 150,306 control chromosomes in the GnomAD database, including 23,160 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 0.50 (23160 hom., cov: 28)
• Consequence: NRXN2 NM_015080.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405
• Publications: 25 publications found

Genes affected

NRXN2 (HGNC:8009): (neurexin 2) This gene encodes a member of the neurexin gene family. The products of these genes function as cell adhesion molecules and receptors in the vertebrate nervous system. These genes utilize two promoters. The majority of transcripts are produced from the upstream promoter and encode alpha-neurexin isoforms while a smaller number of transcripts are produced from the downstream promoter and encode beta-neuresin isoforms. The alpha-neurexins contain epidermal growth factor-like (EGF-like) sequences and laminin G domains, and have been shown to interact with neurexophilins. The beta-neurexins lack EGF-like sequences and contain fewer laminin G domains than alpha-neurexins. Alternative splicing and the use of alternative promoters may generate thousands of transcript variants (PMID: 12036300, PMID: 11944992).[provided by RefSeq, Jun 2010]

NRXN2 Gene-Disease associations (from GenCC):

• autism

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN2	NM_015080.4	c.748+1162A>T		intron_variant	Intron 3 of 22	ENST00000265459.11	NP_055895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN2	ENST00000265459.11	c.748+1162A>T		intron_variant	Intron 3 of 22	5	NM_015080.4	ENSP00000265459.5
NRXN2	ENST00000704782.1	c.748+1162A>T		intron_variant	Intron 2 of 21			ENSP00000516031.1
NRXN2	ENST00000704781.1	c.748+1162A>T		intron_variant	Intron 2 of 21			ENSP00000516029.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 75680 AN: 150192 Hom.: 23163 Cov.: 28

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.504 AC: 75683 AN: 150306 Hom.: 23160 Cov.: 28 AF XY: 0.498 AC XY: 36506 AN XY: 73318

African (AFR) AF: 0.159 AC: 6444 AN: 40562

American (AMR) AF: 0.498 AC: 7550 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 2362 AN: 3466

East Asian (EAS) AF: 0.227 AC: 1149 AN: 5054

South Asian (SAS) AF: 0.588 AC: 2791 AN: 4746

European-Finnish (FIN) AF: 0.583 AC: 5991 AN: 10268

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47277 AN: 67754

Other (OTH) AF: 0.554 AC: 1163 AN: 2098

Alfa AF: 0.587 Hom.: 3530

Bravo AF: 0.478

Asia WGS AF: 0.380 AC: 1323 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.64
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs504915; hg19: chr11-64464085;