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GeneBe

8-32595868-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_013964.5(NRG1):c.141G>A(p.Ser47=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000446 in 1,613,140 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00046 ( 5 hom. )

Consequence

NRG1
NM_013964.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.59
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-32595868-G-A is Benign according to our data. Variant chr8-32595868-G-A is described in ClinVar as [Benign]. Clinvar id is 749108.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.59 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 49 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NRG1NM_013964.5 linkuse as main transcriptc.141G>A p.Ser47= synonymous_variant 2/12 ENST00000405005.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NRG1ENST00000405005.8 linkuse as main transcriptc.141G>A p.Ser47= synonymous_variant 2/121 NM_013964.5 A2Q02297-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000322
AC:
49
AN:
152080
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00374
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00269
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000279
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000643
AC:
161
AN:
250572
Hom.:
1
AF XY:
0.000738
AC XY:
100
AN XY:
135434
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00428
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00258
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000300
Gnomad OTH exome
AF:
0.000328
GnomAD4 exome
AF:
0.000460
AC:
672
AN:
1460942
Hom.:
5
Cov.:
33
AF XY:
0.000530
AC XY:
385
AN XY:
726764
show subpopulations
Gnomad4 AFR exome
AF:
0.0000897
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00433
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00302
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000234
Gnomad4 OTH exome
AF:
0.000580
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000315
AC:
48
AN:
152198
Hom.:
0
Cov.:
32
AF XY:
0.000403
AC XY:
30
AN XY:
74420
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00374
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00270
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000265
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000441
Hom.:
0
Bravo
AF:
0.000238
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000273
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 24, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.70
Cadd
Benign
1.1
Dann
Benign
0.53

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs147561043; hg19: chr8-32453386; API