rs170249

Variant names:

• chr14-79603584-C-A
• rs170249
• NM_001330195.2:c.3445-60194C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-79603584-C-A
• chr14-79603584-C-T

Variant summary

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

The NM_001330195.2(NRXN3):​c.3445-60194C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0835 in 152,076 control chromosomes in the GnomAD database, including 747 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 0.083 (747 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189

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]

LOC105370583 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.3445-60194C>A		intron_variant	Intron 16 of 20	ENST00000335750.7	NP_001317124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.3445-60194C>A		intron_variant	Intron 16 of 20	5	NM_001330195.2	ENSP00000338349.7

Frequencies

GnomAD3 genomes AF: 0.0835 AC: 12694 AN: 151958 Hom.: 747 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0523

Gnomad ASJ AF: 0.0749

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.0730

Gnomad FIN AF: 0.0241

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0515

Gnomad OTH AF: 0.0810

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

GnomAD4 genome AF: 0.0835 AC: 12693 AN: 152076 Hom.: 747 Cov.: 32 AF XY: 0.0823 AC XY: 6124 AN XY: 74372

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.0519

Gnomad4 ASJ AF: 0.0749

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.0724

Gnomad4 FIN AF: 0.0241

Gnomad4 NFE AF: 0.0515

Gnomad4 OTH AF: 0.0802

Alfa AF: 0.0316 Hom.: 34

Bravo AF: 0.0907

Asia WGS AF: 0.112 AC: 391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.47

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: rs170249; hg19: chr14-80069927;