rs8017049

Variant names:

• chr14-78576222-T-C
• rs8017049
• NM_001330195.2:c.758-68898T>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.758-68898T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,148 control chromosomes in the GnomAD database, including 5,827 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 0.21 (5827 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.190
• Publications: 1 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.758-68898T>C		intron_variant	Intron 4 of 20	ENST00000335750.7	NP_001317124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.758-68898T>C		intron_variant	Intron 4 of 20	5	NM_001330195.2	ENSP00000338349.7

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31365 AN: 152030 Hom.: 5790 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0952

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0587

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0847

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.207 AC: 31451 AN: 152148 Hom.: 5827 Cov.: 32 AF XY: 0.202 AC XY: 14994 AN XY: 74406

African (AFR) AF: 0.497 AC: 20593 AN: 41456

American (AMR) AF: 0.109 AC: 1673 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0952 AC: 330 AN: 3468

East Asian (EAS) AF: 0.265 AC: 1367 AN: 5168

South Asian (SAS) AF: 0.118 AC: 569 AN: 4822

European-Finnish (FIN) AF: 0.0587 AC: 623 AN: 10614

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0847 AC: 5759 AN: 68016

Other (OTH) AF: 0.173 AC: 364 AN: 2108

Alfa AF: 0.110 Hom.: 679

Bravo AF: 0.224

Asia WGS AF: 0.218 AC: 757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.81
PhyloP100		0.19
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: rs8017049; hg19: chr14-79042565;