ENST00000520407.5:c.312G>A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7
The ENST00000520407.5(NRG1):c.312G>A(p.Ala104Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000315 in 1,132,770 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 1 hom. )
Consequence
NRG1
ENST00000520407.5 synonymous
ENST00000520407.5 synonymous
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 0.322
Publications
2 publications found
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 6Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
Variant 8-31640296-G-A is Benign according to our data. Variant chr8-31640296-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 98387.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.322 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| NRG1 | NM_013962.3 | c.312G>A | p.Ala104Ala | synonymous_variant | Exon 1 of 5 | NP_039256.2 | ||
| NRG1 | XM_011544512.3 | c.312G>A | p.Ala104Ala | synonymous_variant | Exon 1 of 13 | XP_011542814.2 | ||
| NRG1 | XM_017013367.2 | c.312G>A | p.Ala104Ala | synonymous_variant | Exon 1 of 11 | XP_016868856.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| NRG1 | ENST00000520407.5 | c.312G>A | p.Ala104Ala | synonymous_variant | Exon 1 of 5 | 1 | ENSP00000434640.1 | |||
| NRG1 | ENST00000650866.1 | c.37+865G>A | intron_variant | Intron 1 of 12 | ENSP00000499045.1 | |||||
| NRG1 | ENST00000652698.1 | c.37+865G>A | intron_variant | Intron 1 of 11 | ENSP00000499008.1 |
Frequencies
GnomAD3 genomes 0.00138 AC: 205AN: 148074Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
205
AN:
148074
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00 AC: 0AN: 262 AF XY: 0.00
GnomAD2 exomes
AF:
AC:
0
AN:
262
AF XY:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000153 AC: 151AN: 984592Hom.: 1 Cov.: 34 AF XY: 0.000121 AC XY: 56AN XY: 463962 show subpopulations
GnomAD4 exome
AF:
AC:
151
AN:
984592
Hom.:
Cov.:
34
AF XY:
AC XY:
56
AN XY:
463962
show subpopulations
African (AFR)
AF:
AC:
129
AN:
19374
American (AMR)
AF:
AC:
1
AN:
5374
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
9776
East Asian (EAS)
AF:
AC:
0
AN:
17506
South Asian (SAS)
AF:
AC:
0
AN:
18620
European-Finnish (FIN)
AF:
AC:
0
AN:
16658
Middle Eastern (MID)
AF:
AC:
2
AN:
2390
European-Non Finnish (NFE)
AF:
AC:
0
AN:
858586
Other (OTH)
AF:
AC:
19
AN:
36308
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.520
Heterozygous variant carriers
0
9
19
28
38
47
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00139 AC: 206AN: 148178Hom.: 0 Cov.: 32 AF XY: 0.00130 AC XY: 94AN XY: 72198 show subpopulations
GnomAD4 genome
AF:
AC:
206
AN:
148178
Hom.:
Cov.:
32
AF XY:
AC XY:
94
AN XY:
72198
show subpopulations
African (AFR)
AF:
AC:
201
AN:
41162
American (AMR)
AF:
AC:
3
AN:
14924
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3398
East Asian (EAS)
AF:
AC:
0
AN:
5090
South Asian (SAS)
AF:
AC:
0
AN:
4822
European-Finnish (FIN)
AF:
AC:
0
AN:
9126
Middle Eastern (MID)
AF:
AC:
0
AN:
290
European-Non Finnish (NFE)
AF:
AC:
2
AN:
66388
Other (OTH)
AF:
AC:
0
AN:
2066
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
12
23
35
46
58
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1Other:1
Sep 01, 2022
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
NRG1: BP4, BP7 -
-
Psychiatry Genetics Yale University
Significance:not provided
Review Status:no classification provided
Collection Method:literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Uncertain
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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