rs17664708

Variant names:

• chr8-32579499-C-T
• rs17664708
• NM_013964.5:c.101-16329C>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.101-16329C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0998 in 152,096 control chromosomes in the GnomAD database, including 1,112 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 0.10 (1112 hom., cov: 31)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.413
• Publications: 12 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 (AMR) allele frequency at 95% confidence interval = 0.232 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.101-16329C>T		intron	N/A	NP_039258.1
	NRG1	NM_013956.5		c.101-16329C>T		intron	N/A	NP_039250.2
	NRG1	NM_013957.5		c.101-16329C>T		intron	N/A	NP_039251.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	ENST00000405005.8	TSL:1 MANE Select	c.101-16329C>T		intron	N/A	ENSP00000384620.2
	NRG1	ENST00000287842.7	TSL:1	c.101-16329C>T		intron	N/A	ENSP00000287842.4
	NRG1	ENST00000356819.7	TSL:1	c.101-16329C>T		intron	N/A	ENSP00000349275.6

Frequencies

GnomAD3 genomes AF: 0.0998 AC: 15162 AN: 151978 Hom.: 1107 Cov.: 31

Gnomad AFR AF: 0.0267

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.0649

Gnomad EAS AF: 0.0475

Gnomad SAS AF: 0.0526

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0980

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

GnomAD4 genome AF: 0.0998 AC: 15176 AN: 152096 Hom.: 1112 Cov.: 31 AF XY: 0.104 AC XY: 7760 AN XY: 74340

African (AFR) AF: 0.0266 AC: 1106 AN: 41544

American (AMR) AF: 0.238 AC: 3639 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0649 AC: 225 AN: 3468

East Asian (EAS) AF: 0.0474 AC: 245 AN: 5164

South Asian (SAS) AF: 0.0529 AC: 255 AN: 4822

European-Finnish (FIN) AF: 0.177 AC: 1872 AN: 10550

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7514 AN: 67972

Other (OTH) AF: 0.102 AC: 215 AN: 2104

Alfa AF: 0.110 Hom.: 655

Bravo AF: 0.106

Asia WGS AF: 0.0660 AC: 228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.57
DANN	Benign	0.27
PhyloP100		-0.41
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: rs17664708; hg19: chr8-32437017;