chr8-32767310-A-G

Variant summary

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

The NM_013964.5(NRG1):​c.*2908A>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 0.385 in 151,992 control chromosomes in the GnomAD database, including 11,514 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 0.38 ( 11514 hom., cov: 32)
Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

NRG1
NM_013964.5 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.105

Publications

11 publications found
Variant links:
Genes affected
NRG1 (HGNC:7997): (neuregulin 1) The protein encoded by this gene is a membrane glycoprotein that mediates cell-cell signaling and plays a critical role in the growth and development of multiple organ systems. An extraordinary variety of different isoforms are produced from this gene through alternative promoter usage and splicing. These isoforms are expressed in a tissue-specific manner and differ significantly in their structure, and are classified as types I, II, III, IV, V and VI. Dysregulation of this gene has been linked to diseases such as cancer, schizophrenia, and bipolar disorder (BPD). [provided by RefSeq, Apr 2016]
NRG1 Gene-Disease associations (from GenCC):
  • schizophrenia 6
    Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

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=-0.8).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NRG1NM_013964.5 linkc.*2908A>G 3_prime_UTR_variant Exon 12 of 12 ENST00000405005.8 NP_039258.1 Q02297-1Q6PK61

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NRG1ENST00000405005.8 linkc.*2908A>G 3_prime_UTR_variant Exon 12 of 12 1 NM_013964.5 ENSP00000384620.2 Q02297-1

Frequencies

GnomAD3 genomes
AF:
0.385
AC:
58435
AN:
151870
Hom.:
11496
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.386
Gnomad AMI
AF:
0.499
Gnomad AMR
AF:
0.307
Gnomad ASJ
AF:
0.373
Gnomad EAS
AF:
0.199
Gnomad SAS
AF:
0.341
Gnomad FIN
AF:
0.338
Gnomad MID
AF:
0.443
Gnomad NFE
AF:
0.424
Gnomad OTH
AF:
0.396
GnomAD4 exome
AF:
0.500
AC:
2
AN:
4
Hom.:
0
Cov.:
0
AF XY:
0.500
AC XY:
2
AN XY:
4
show subpopulations
African (AFR)
AF:
0.500
AC:
1
AN:
2
American (AMR)
AC:
0
AN:
0
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AC:
0
AN:
0
South Asian (SAS)
AC:
0
AN:
0
European-Finnish (FIN)
AC:
0
AN:
0
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
0.500
AC:
1
AN:
2
Other (OTH)
AC:
0
AN:
0
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.385
AC:
58490
AN:
151988
Hom.:
11514
Cov.:
32
AF XY:
0.376
AC XY:
27897
AN XY:
74256
show subpopulations
African (AFR)
AF:
0.386
AC:
15993
AN:
41426
American (AMR)
AF:
0.307
AC:
4679
AN:
15256
Ashkenazi Jewish (ASJ)
AF:
0.373
AC:
1293
AN:
3468
East Asian (EAS)
AF:
0.199
AC:
1027
AN:
5166
South Asian (SAS)
AF:
0.342
AC:
1646
AN:
4816
European-Finnish (FIN)
AF:
0.338
AC:
3559
AN:
10542
Middle Eastern (MID)
AF:
0.452
AC:
133
AN:
294
European-Non Finnish (NFE)
AF:
0.424
AC:
28857
AN:
68000
Other (OTH)
AF:
0.402
AC:
848
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1825
3649
5474
7298
9123
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
548
1096
1644
2192
2740
<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:
0.403
Hom.:
15775
Bravo
AF:
0.379
Asia WGS
AF:
0.298
AC:
1041
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
8.1
DANN
Benign
0.68
PhyloP100
0.10

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs3735781; hg19: chr8-32624828; API