rs7825588

chr8-32646882-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013964.5(NRG1):c.502+29997G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 984,474 control chromosomes in the GnomAD database, including 6,286 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 0.11 (1040 hom., cov: 30)
  • Exomes 𝑓: 0.11 (5246 hom.)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.78

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=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG1	NM_013964.5	c.502+29997G>A		intron_variant		ENST00000405005.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1	ENST00000405005.8	c.502+29997G>A		intron_variant		1	NM_013964.5	A2

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16860 AN: 151264 Hom.: 1039 Cov.: 30

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0747

Gnomad AMR AF: 0.0867

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0634

Gnomad FIN AF: 0.0975

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.110

GnomAD4 exome AF: 0.112 AC: 92983 AN: 833092 Hom.: 5246 Cov.: 29 AF XY: 0.112 AC XY: 43060 AN XY: 384702

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.0661

Gnomad4 ASJ exome AF: 0.174

Gnomad4 EAS exome AF: 0.000826

Gnomad4 SAS exome AF: 0.0739

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.112

Gnomad4 OTH exome AF: 0.108

GnomAD4 genome AF: 0.111 AC: 16869 AN: 151382 Hom.: 1040 Cov.: 30 AF XY: 0.108 AC XY: 8020 AN XY: 73926

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.0866

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.0628

Gnomad4 FIN AF: 0.0975

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.108

Alfa AF: 0.112 Hom.: 1309

Bravo AF: 0.115

Asia WGS AF: 0.0460 AC: 162 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	8.5
Dann	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7825588; hg19: chr8-32504401;