chr14-78567834-A-C

Variant names:

• chr14-78567834-A-C
• rs7157915
• NM_001330195.2:c.758-77286A>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.758-77286A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0611 in 152,120 control chromosomes in the GnomAD database, including 421 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 0.061 (421 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330195.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN3	NM_001330195.2	MANE Select	c.758-77286A>C		intron	N/A	NP_001317124.1
	NRXN3	NM_001366425.1		c.758-77286A>C		intron	N/A	NP_001353354.1
	NRXN3	NM_001366426.1		c.770-77286A>C		intron	N/A	NP_001353355.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN3	ENST00000335750.7	TSL:5 MANE Select	c.758-77286A>C		intron	N/A	ENSP00000338349.7
	NRXN3	ENST00000554719.5	TSL:1	c.-362-77286A>C		intron	N/A	ENSP00000451648.1
	NRXN3	ENST00000634499.2	TSL:5	c.770-77286A>C		intron	N/A	ENSP00000488920.2

Frequencies

GnomAD3 genomes AF: 0.0609 AC: 9257 AN: 152002 Hom.: 412 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0397

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.0694

Gnomad FIN AF: 0.00829

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0311

Gnomad OTH AF: 0.0455

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

GnomAD4 genome AF: 0.0611 AC: 9288 AN: 152120 Hom.: 421 Cov.: 32 AF XY: 0.0598 AC XY: 4450 AN XY: 74364

African (AFR) AF: 0.124 AC: 5159 AN: 41462

American (AMR) AF: 0.0396 AC: 606 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 87 AN: 3466

East Asian (EAS) AF: 0.134 AC: 691 AN: 5152

South Asian (SAS) AF: 0.0703 AC: 338 AN: 4806

European-Finnish (FIN) AF: 0.00829 AC: 88 AN: 10618

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0311 AC: 2118 AN: 67998

Other (OTH) AF: 0.0450 AC: 95 AN: 2112

Alfa AF: 0.0457 Hom.: 49

Bravo AF: 0.0667

Asia WGS AF: 0.108 AC: 375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.033
DANN	Benign	0.60
PhyloP100		-1.4
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: rs7157915; hg19: chr14-79034177;