chr8-31639999-C-G
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2
The ENST00000520407.5(NRG1):c.15C>G(p.Arg5=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000544 in 1,122,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000057 ( 0 hom. )
Consequence
NRG1
ENST00000520407.5 synonymous
ENST00000520407.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.586
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 8-31639999-C-G is Benign according to our data. Variant chr8-31639999-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3042743.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.586 with no splicing effect.
BS2
?
High AC in GnomAd at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NRG1 | NM_013962.3 | c.15C>G | p.Arg5= | synonymous_variant | 1/5 | ||
NRG1 | XM_011544512.3 | c.15C>G | p.Arg5= | synonymous_variant | 1/13 | ||
NRG1 | XM_017013367.2 | c.15C>G | p.Arg5= | synonymous_variant | 1/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NRG1 | ENST00000520407.5 | c.15C>G | p.Arg5= | synonymous_variant | 1/5 | 1 | |||
NRG1 | ENST00000519301.6 | c.37+568C>G | intron_variant | 5 | |||||
NRG1 | ENST00000650866.1 | c.37+568C>G | intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000402 AC: 6AN: 149350Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
6
AN:
149350
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:
GnomAD3 exomes AF: 0.000327 AC: 2AN: 6118Hom.: 0 AF XY: 0.000617 AC XY: 2AN XY: 3240
GnomAD3 exomes
AF:
AC:
2
AN:
6118
Hom.:
AF XY:
AC XY:
2
AN XY:
3240
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000565 AC: 55AN: 972672Hom.: 0 Cov.: 35 AF XY: 0.0000632 AC XY: 29AN XY: 458540
GnomAD4 exome
AF:
AC:
55
AN:
972672
Hom.:
Cov.:
35
AF XY:
AC XY:
29
AN XY:
458540
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000402 AC: 6AN: 149350Hom.: 0 Cov.: 32 AF XY: 0.0000275 AC XY: 2AN XY: 72830
GnomAD4 genome
?
AF:
AC:
6
AN:
149350
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
72830
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
NRG1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 21, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at