NM_001010848.4:c.1028-9145G>C

Variant summary

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

The NM_001010848.4(NRG3):​c.1028-9145G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,860 control chromosomes in the GnomAD database, including 15,997 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 0.45 ( 15997 hom., cov: 31)

Consequence

NRG3
NM_001010848.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.236

Publications

2 publications found
Variant links:
Genes affected
NRG3 (HGNC:7999): (neuregulin 3) This gene is a member of the neuregulin gene family. This gene family encodes ligands for the transmembrane tyrosine kinase receptors ERBB3 and ERBB4 - members of the epidermal growth factor receptor family. Ligand binding activates intracellular signaling cascades and the induction of cellular responses including proliferation, migration, differentiation, and survival or apoptosis. This gene encodes neuregulin 3 (NRG3). NRG3 has been shown to activate the tyrosine phosphorylation of its cognate receptor, ERBB4, and is thought to influence neuroblast proliferation, migration and differentiation by signalling through ERBB4. NRG3 also promotes mammary differentiation during embryogenesis. Linkage studies have implicated this gene as a susceptibility locus for schizophrenia and schizoaffective disorder. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described but their biological validity has not been verified.[provided by RefSeq, Sep 2009]

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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=-0.92).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NRG3NM_001010848.4 linkc.1028-9145G>C intron_variant Intron 3 of 8 ENST00000372141.7 NP_001010848.2 P56975-4B9EGV5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NRG3ENST00000372141.7 linkc.1028-9145G>C intron_variant Intron 3 of 8 1 NM_001010848.4 ENSP00000361214.2 P56975-4

Frequencies

GnomAD3 genomes
AF:
0.454
AC:
68953
AN:
151740
Hom.:
15988
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.480
Gnomad AMI
AF:
0.223
Gnomad AMR
AF:
0.381
Gnomad ASJ
AF:
0.495
Gnomad EAS
AF:
0.124
Gnomad SAS
AF:
0.456
Gnomad FIN
AF:
0.413
Gnomad MID
AF:
0.405
Gnomad NFE
AF:
0.488
Gnomad OTH
AF:
0.441
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.454
AC:
68990
AN:
151860
Hom.:
15997
Cov.:
31
AF XY:
0.448
AC XY:
33242
AN XY:
74224
show subpopulations
African (AFR)
AF:
0.480
AC:
19863
AN:
41388
American (AMR)
AF:
0.381
AC:
5808
AN:
15260
Ashkenazi Jewish (ASJ)
AF:
0.495
AC:
1715
AN:
3466
East Asian (EAS)
AF:
0.125
AC:
643
AN:
5152
South Asian (SAS)
AF:
0.456
AC:
2189
AN:
4796
European-Finnish (FIN)
AF:
0.413
AC:
4360
AN:
10548
Middle Eastern (MID)
AF:
0.408
AC:
120
AN:
294
European-Non Finnish (NFE)
AF:
0.488
AC:
33159
AN:
67932
Other (OTH)
AF:
0.440
AC:
930
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1874
3747
5621
7494
9368
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
636
1272
1908
2544
3180
<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:
0.295
Hom.:
688
Bravo
AF:
0.449
Asia WGS
AF:
0.299
AC:
1043
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
4.6
DANN
Benign
0.57
PhyloP100
0.24
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

Publications

Other links and lift over

dbSNP: rs2483295; hg19: chr10-84616022; API