dbSNP rs983795: NRXN3:c.-703-11178G>A (chr14-78231213-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001330195.2(NRXN3):c.-703-11178G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,116 control chromosomes in the GnomAD database, including 1,269 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 0.12 ( 1267 hom., cov: 32)

Exomes 𝑓: 0.31 ( 2 hom. )

Consequence

NRXN3
NM_001330195.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.199

Publications

3 publications found

Variant links:

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 links:

RPS26P48 (HGNC:35519): (ribosomal protein S26 pseudogene 48)

RPS26P48 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.148 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NRXN3	NM_001330195.2	MANE Select	c.-703-11178G>A	intron	N/A	NP_001317124.1	A0A0A0MR89
NRXN3	NM_001366425.1		c.-703-11178G>A	intron	N/A	NP_001353354.1
NRXN3	NM_001366426.1		c.-703-11178G>A	intron	N/A	NP_001353355.1	A0A0U1RQC5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NRXN3	ENST00000335750.7	TSL:5 MANE Select	c.-703-11178G>A	intron	N/A	ENSP00000338349.7	A0A0A0MR89
NRXN3	ENST00000634499.2	TSL:5	c.-703-11178G>A	intron	N/A	ENSP00000488920.2	A0A0U1RQC5
RPS26P48	ENST00000491713.1	TSL:6	n.*68C>T	downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

18924

AN:

151970

Hom.:

1263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0876

Gnomad AMI

AF:

0.265

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.157

Gnomad SAS

AF:

0.139

Gnomad FIN

AF:

0.181

Gnomad MID

AF:

0.147

Gnomad NFE

AF:

0.137

Gnomad OTH

AF:

0.136

GnomAD4 exome

AF:

0.308

AC:

AN:

Hom.:

AF XY:

0.364

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.200

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.375

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.125

AC:

18952

AN:

152090

Hom.:

1267

Cov.:

AF XY:

0.128

AC XY:

9523

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0879

AC:

3648

AN:

41498

American (AMR)

AF:

0.103

AC:

1568

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

438

AN:

3472

East Asian (EAS)

AF:

0.157

AC:

813

AN:

5172

South Asian (SAS)

AF:

0.139

AC:

665

AN:

4800

European-Finnish (FIN)

AF:

0.181

AC:

1919

AN:

10582

Middle Eastern (MID)

AF:

0.147

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.137

AC:

9321

AN:

67974

Other (OTH)

AF:

0.140

AC:

297

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

851

1701

2552

3402

4253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

218

436

654

872

1090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.124

Hom.:

1886

Bravo

AF:

0.116

Asia WGS

AF:

0.152

AC:

532

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.70

(source)

DANN

Benign

0.66

PhyloP100

-0.20

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over