8-32584838-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013964.5(NRG1):​c.101-10990A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,112 control chromosomes in the GnomAD database, including 5,122 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 0.26 ( 5122 hom., cov: 33)

Consequence

NRG1
NM_013964.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0470
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NRG1NM_013964.5 linkc.101-10990A>G intron_variant Intron 1 of 11 ENST00000405005.8 NP_039258.1 Q02297-1Q6PK61

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NRG1ENST00000405005.8 linkc.101-10990A>G intron_variant Intron 1 of 11 1 NM_013964.5 ENSP00000384620.2 Q02297-1

Frequencies

GnomAD3 genomes
AF:
0.256
AC:
38976
AN:
151994
Hom.:
5118
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.244
Gnomad AMI
AF:
0.303
Gnomad AMR
AF:
0.199
Gnomad ASJ
AF:
0.267
Gnomad EAS
AF:
0.168
Gnomad SAS
AF:
0.332
Gnomad FIN
AF:
0.323
Gnomad MID
AF:
0.237
Gnomad NFE
AF:
0.267
Gnomad OTH
AF:
0.245
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.256
AC:
39004
AN:
152112
Hom.:
5122
Cov.:
33
AF XY:
0.257
AC XY:
19104
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.244
Gnomad4 AMR
AF:
0.200
Gnomad4 ASJ
AF:
0.267
Gnomad4 EAS
AF:
0.168
Gnomad4 SAS
AF:
0.332
Gnomad4 FIN
AF:
0.323
Gnomad4 NFE
AF:
0.267
Gnomad4 OTH
AF:
0.243
Alfa
AF:
0.245
Hom.:
2446
Bravo
AF:
0.244

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
2.7
DANN
Benign
0.74

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: rs10954859; hg19: chr8-32442356; API