rs6982890

Variant names:

• chr8-32757580-C-T
• rs6982890
• NM_013964.5:c.930+1051C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013964.5(NRG1):​c.930+1051C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,122 control chromosomes in the GnomAD database, including 3,203 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 0.20 (3203 hom., cov: 32)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244
• Publications: 7 publications found

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]

NRG1 Gene-Disease associations (from GenCC):

• schizophrenia 6

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013964.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	NM_013964.5	MANE Select	c.930+1051C>T		intron	N/A	NP_039258.1
	NRG1	NM_001322205.2		c.1110+1051C>T		intron	N/A	NP_001309134.1
	NRG1	NM_013956.5		c.945+1051C>T		intron	N/A	NP_039250.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	ENST00000405005.8	TSL:1 MANE Select	c.930+1051C>T		intron	N/A	ENSP00000384620.2
	NRG1	ENST00000287842.7	TSL:1	c.945+1051C>T		intron	N/A	ENSP00000287842.4
	NRG1	ENST00000356819.7	TSL:1	c.921+1051C>T		intron	N/A	ENSP00000349275.6

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29840 AN: 152004 Hom.: 3186 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.196 AC: 29877 AN: 152122 Hom.: 3203 Cov.: 32 AF XY: 0.189 AC XY: 14086 AN XY: 74370

African (AFR) AF: 0.140 AC: 5822 AN: 41510

American (AMR) AF: 0.171 AC: 2612 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 565 AN: 3466

East Asian (EAS) AF: 0.198 AC: 1020 AN: 5162

South Asian (SAS) AF: 0.244 AC: 1174 AN: 4818

European-Finnish (FIN) AF: 0.114 AC: 1201 AN: 10580

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16667 AN: 67976

Other (OTH) AF: 0.225 AC: 475 AN: 2114

Alfa AF: 0.227 Hom.: 14279

Bravo AF: 0.196

Asia WGS AF: 0.248 AC: 862 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.30
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6982890; hg19: chr8-32615098;