rs3757933

chr8-32747325-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.700+5250G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 151,824 control chromosomes in the GnomAD database, including 4,838 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 0.23 (4838 hom., cov: 30)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.151

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG1	NM_013964.5	c.700+5250G>A		intron_variant		ENST00000405005.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1	ENST00000405005.8	c.700+5250G>A		intron_variant		1	NM_013964.5	A2

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35497 AN: 151706 Hom.: 4828 Cov.: 30

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.234 AC: 35529 AN: 151824 Hom.: 4838 Cov.: 30 AF XY: 0.238 AC XY: 17634 AN XY: 74188

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.225

Alfa AF: 0.211 Hom.: 577

Bravo AF: 0.245

Asia WGS AF: 0.279 AC: 970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.81
Dann	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3757933; hg19: chr8-32604843;