chr14-78771006-A-C

Variant names:

• chr14-78771006-A-C
• rs8011930
• NM_001330195.2:c.2045-32614A>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.2045-32614A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0682 in 152,282 control chromosomes in the GnomAD database, including 459 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 0.068 (459 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.2045-32614A>C		intron_variant	Intron 8 of 20	ENST00000335750.7	NP_001317124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.2045-32614A>C		intron_variant	Intron 8 of 20	5	NM_001330195.2	ENSP00000338349.7

Frequencies

GnomAD3 genomes AF: 0.0682 AC: 10385 AN: 152164 Hom.: 459 Cov.: 32

Gnomad AFR AF: 0.0239

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0543

Gnomad ASJ AF: 0.0361

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0821

Gnomad OTH AF: 0.0750

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

GnomAD4 genome AF: 0.0682 AC: 10391 AN: 152282 Hom.: 459 Cov.: 32 AF XY: 0.0720 AC XY: 5363 AN XY: 74458

African (AFR) AF: 0.0240 AC: 998 AN: 41570

American (AMR) AF: 0.0543 AC: 830 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0361 AC: 125 AN: 3466

East Asian (EAS) AF: 0.102 AC: 526 AN: 5174

South Asian (SAS) AF: 0.141 AC: 677 AN: 4816

European-Finnish (FIN) AF: 0.136 AC: 1441 AN: 10608

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0821 AC: 5585 AN: 68032

Other (OTH) AF: 0.0762 AC: 161 AN: 2114

Alfa AF: 0.0735 Hom.: 790

Bravo AF: 0.0575

Asia WGS AF: 0.126 AC: 436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.8
DANN	Benign	0.74
PhyloP100		0.20
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: rs8011930; hg19: chr14-79237349;