rs12547858

chr8-32629535-C-T

Variant summary

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

The NM_013964.5(NRG1):c.502+12650C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,108 control chromosomes in the GnomAD database, including 2,164 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 0.15 (2164 hom., cov: 32)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229

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 = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG1	NM_013964.5	c.502+12650C>T		intron_variant		ENST00000405005.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1	ENST00000405005.8	c.502+12650C>T		intron_variant		1	NM_013964.5	A2

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22820 AN: 151990 Hom.: 2164 Cov.: 32

Gnomad AFR AF: 0.0355

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.150 AC: 22835 AN: 152108 Hom.: 2164 Cov.: 32 AF XY: 0.154 AC XY: 11480 AN XY: 74320

Gnomad4 AFR AF: 0.0354

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.157

Alfa AF: 0.176 Hom.: 2980

Bravo AF: 0.140

Asia WGS AF: 0.160 AC: 554 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.5
Dann	Benign	0.24

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12547858; hg19: chr8-32487053;