rs7820929

chr8-31785294-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG1	NM_001159995.3	c.37+145863C>G		intron_variant
NRG1	NM_001159999.3	c.37+145863C>G		intron_variant
NRG1	NM_001160001.3	c.37+145863C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1	ENST00000520407.5	c.745+144565C>G		intron_variant		1
NRG1	ENST00000519301.6	c.37+145863C>G		intron_variant		5
NRG1	ENST00000523534.5	c.304+144565C>G		intron_variant		5

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

Gnomad4 AFR AF: 0.685

Gnomad4 AMR AF: 0.768

Gnomad4 ASJ AF: 0.692

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.895

Gnomad4 FIN AF: 0.822

Gnomad4 NFE AF: 0.749

Gnomad4 OTH AF: 0.715

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	5.7
Dann	Benign	0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7820929; hg19: chr8-31642810;