rs221497

Positions:

• chr14-79622137-G-A
• chr14-79622137-G-C

Variant summary

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

The NM_001330195.2(NRXN3):​c.3445-41641G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,054 control chromosomes in the GnomAD database, including 2,105 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 0.14 (2105 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.563

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.3445-41641G>A		intron_variant		ENST00000335750.7	NP_001317124.1
LOC105370583	XR_001751001.3	n.217+10141C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.3445-41641G>A		intron_variant		5	NM_001330195.2	ENSP00000338349	P1
	ENST00000553812.1	n.138+10141C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21774 AN: 151936 Hom.: 2107 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0866

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0850

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.143 AC: 21790 AN: 152054 Hom.: 2105 Cov.: 32 AF XY: 0.145 AC XY: 10767 AN XY: 74312

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.0863

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.0850

Gnomad4 OTH AF: 0.142

Alfa AF: 0.100 Hom.: 1535

Bravo AF: 0.146

Asia WGS AF: 0.139 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.3
DANN	Benign	0.48

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: rs221497; hg19: chr14-80088480;