rs1023911

Variant summary

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

The ENST00000520407.5(NRG1):​c.745+326887A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 152,084 control chromosomes in the GnomAD database, including 34,543 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 0.63 ( 34543 hom., cov: 32)

Consequence

NRG1
ENST00000520407.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.233
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NRG1NM_001159995.3 linkuse as main transcriptc.37+328185A>G intron_variant
NRG1NM_001159999.3 linkuse as main transcriptc.37+328185A>G intron_variant
NRG1NM_001160001.3 linkuse as main transcriptc.37+328185A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NRG1ENST00000520407.5 linkuse as main transcriptc.745+326887A>G intron_variant 1 Q02297-9
NRG1ENST00000519301.6 linkuse as main transcriptc.37+328185A>G intron_variant 5 Q02297-11
NRG1ENST00000523534.5 linkuse as main transcriptc.304+326887A>G intron_variant 5

Frequencies

GnomAD3 genomes
AF:
0.630
AC:
95668
AN:
151966
Hom.:
34523
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.262
Gnomad AMI
AF:
0.817
Gnomad AMR
AF:
0.711
Gnomad ASJ
AF:
0.761
Gnomad EAS
AF:
0.374
Gnomad SAS
AF:
0.711
Gnomad FIN
AF:
0.806
Gnomad MID
AF:
0.712
Gnomad NFE
AF:
0.810
Gnomad OTH
AF:
0.657
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.629
AC:
95712
AN:
152084
Hom.:
34543
Cov.:
32
AF XY:
0.630
AC XY:
46870
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.262
Gnomad4 AMR
AF:
0.712
Gnomad4 ASJ
AF:
0.761
Gnomad4 EAS
AF:
0.374
Gnomad4 SAS
AF:
0.711
Gnomad4 FIN
AF:
0.806
Gnomad4 NFE
AF:
0.810
Gnomad4 OTH
AF:
0.660
Alfa
AF:
0.755
Hom.:
21752
Bravo
AF:
0.603
Asia WGS
AF:
0.582
AC:
2022
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
2.7
DANN
Benign
0.78

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: rs1023911; hg19: chr8-31825132; API