rs2439312

chr8-32554841-A-G

Variant summary

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

The NM_013964.5(NRG1):c.100+6015A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 151,834 control chromosomes in the GnomAD database, including 46,935 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 0.78 (46935 hom., cov: 30)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.467

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG1	NM_013964.5	c.100+6015A>G		intron_variant		ENST00000405005.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1	ENST00000405005.8	c.100+6015A>G		intron_variant		1	NM_013964.5	A2

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119063 AN: 151714 Hom.: 46892 Cov.: 30

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.794

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

GnomAD4 genome AF: 0.785 AC: 119162 AN: 151834 Hom.: 46935 Cov.: 30 AF XY: 0.785 AC XY: 58249 AN XY: 74170

Gnomad4 AFR AF: 0.763

Gnomad4 AMR AF: 0.865

Gnomad4 ASJ AF: 0.767

Gnomad4 EAS AF: 0.800

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.823

Gnomad4 NFE AF: 0.782

Gnomad4 OTH AF: 0.790

Alfa AF: 0.784 Hom.: 108949

Bravo AF: 0.791

Asia WGS AF: 0.710 AC: 2472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	6.0
Dann	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2439312; hg19: chr8-32412359;