rs12680129

chr8-32585627-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.101-10201A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0938 in 152,266 control chromosomes in the GnomAD database, including 1,819 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 0.094 (1819 hom., cov: 33)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG1	NM_013964.5	c.101-10201A>G		intron_variant		ENST00000405005.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1	ENST00000405005.8	c.101-10201A>G		intron_variant		1	NM_013964.5	A2

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14271 AN: 152148 Hom.: 1814 Cov.: 33

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0819

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.0631

Gnomad FIN AF: 0.0165

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0170

Gnomad OTH AF: 0.0807

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

GnomAD4 genome AF: 0.0938 AC: 14289 AN: 152266 Hom.: 1819 Cov.: 33 AF XY: 0.0963 AC XY: 7173 AN XY: 74448

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.0819

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.0623

Gnomad4 FIN AF: 0.0165

Gnomad4 NFE AF: 0.0170

Gnomad4 OTH AF: 0.0784

Alfa AF: 0.0555 Hom.: 304

Bravo AF: 0.108

Asia WGS AF: 0.240 AC: 837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.97
Dann	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12680129; hg19: chr8-32443145;