dbSNP rs8421: NRG3:c.*1260A>G (chr10-82986865-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001010848.4(NRG3):c.*1260A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,100 control chromosomes in the GnomAD database, including 16,612 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 ( 16612 hom., cov: 33)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

NRG3
NM_001010848.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.68

Publications

4 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]

NRG3 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=-0.77).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010848.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NRG3	NM_001010848.4	MANE Select	c.*1260A>G	3_prime_UTR	Exon 9 of 9	NP_001010848.2	P56975-4
NRG3	NM_001370084.1		c.*1260A>G	3_prime_UTR	Exon 10 of 10	NP_001357013.1	D9ZHP6
NRG3	NM_001370081.1		c.*1260A>G	3_prime_UTR	Exon 9 of 9	NP_001357010.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NRG3	ENST00000372141.7	TSL:1 MANE Select	c.*1260A>G	3_prime_UTR	Exon 9 of 9	ENSP00000361214.2	P56975-4
NRG3	ENST00000372142.6	TSL:1	c.*1260A>G	3_prime_UTR	Exon 11 of 11	ENSP00000361215.2	P56975-3
NRG3	ENST00000545131.5	TSL:5	c.*1260A>G	3_prime_UTR	Exon 7 of 7	ENSP00000441201.1	D9ZHQ8

Frequencies

GnomAD3 genomes

AF:

0.446

AC:

67825

AN:

151978

Hom.:

16612

Cov.:

show subpopulations

Gnomad AFR

AF:

0.264

Gnomad AMI

AF:

0.609

Gnomad AMR

AF:

0.418

Gnomad ASJ

AF:

0.581

Gnomad EAS

AF:

0.226

Gnomad SAS

AF:

0.406

Gnomad FIN

AF:

0.452

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.572

Gnomad OTH

AF:

0.487

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

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)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.650

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.446

AC:

67844

AN:

152096

Hom.:

16612

Cov.:

AF XY:

0.439

AC XY:

32683

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.264

AC:

10936

AN:

41494

American (AMR)

AF:

0.417

AC:

6377

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.581

AC:

2014

AN:

3466

East Asian (EAS)

AF:

0.226

AC:

1171

AN:

5170

South Asian (SAS)

AF:

0.407

AC:

1964

AN:

4822

European-Finnish (FIN)

AF:

0.452

AC:

4772

AN:

10564

Middle Eastern (MID)

AF:

0.517

AC:

152

AN:

294

European-Non Finnish (NFE)

AF:

0.572

AC:

38874

AN:

67966

Other (OTH)

AF:

0.487

AC:

1029

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1831

3662

5493

7324

9155

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

626

1252

1878

2504

3130

<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:

0.523

Hom.:

60389

Bravo

AF:

0.436

Asia WGS

AF:

0.330

AC:

1144

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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