rs7820929

Variant names:

• chr8-31785294-C-G
• rs7820929
• ENST00000520407.5:c.745+144565C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000520407.5(NRG1):​c.745+144565C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 151,982 control chromosomes in the GnomAD database, including 43,205 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 0.75 (43205 hom., cov: 31)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.637
• Publications: 0 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 6

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000520407.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	NM_001159999.3		c.37+145863C>G		intron	N/A	NP_001153471.1
	NRG1	NM_001159995.3		c.37+145863C>G		intron	N/A	NP_001153467.1
	NRG1	NM_001160001.3		c.37+145863C>G		intron	N/A	NP_001153473.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	ENST00000520407.5	TSL:1	c.745+144565C>G		intron	N/A	ENSP00000434640.1
	NRG1	ENST00000523534.5	TSL:5	c.304+144565C>G		intron	N/A	ENSP00000429067.1
	NRG1	ENST00000650866.1		c.37+145863C>G		intron	N/A	ENSP00000499045.1

Frequencies

GnomAD3 genomes AF: 0.750 AC: 113901 AN: 151864 Hom.: 43156 Cov.: 31

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.896

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.712

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.750 AC: 114007 AN: 151982 Hom.: 43205 Cov.: 31 AF XY: 0.759 AC XY: 56408 AN XY: 74292

African (AFR) AF: 0.685 AC: 28353 AN: 41418

American (AMR) AF: 0.768 AC: 11725 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2401 AN: 3472

East Asian (EAS) AF: 0.994 AC: 5129 AN: 5158

South Asian (SAS) AF: 0.895 AC: 4304 AN: 4810

European-Finnish (FIN) AF: 0.822 AC: 8708 AN: 10600

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.749 AC: 50851 AN: 67936

Other (OTH) AF: 0.715 AC: 1511 AN: 2112

Alfa AF: 0.754 Hom.: 5428

Bravo AF: 0.740

Asia WGS AF: 0.928 AC: 3225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.7
DANN	Benign	0.33
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7820929; hg19: chr8-31642810;