8-32553698-C-T

Variant names:

• chr8-32553698-C-T
• rs16879552
• NM_013964.5:c.100+4872C>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.100+4872C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,026 control chromosomes in the GnomAD database, including 2,086 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 0.11 (2086 hom., cov: 33)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.426
• Publications: 36 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.578 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.100+4872C>T		intron	N/A	NP_039258.1
	NRG1	NM_013956.5		c.100+4872C>T		intron	N/A	NP_039250.2
	NRG1	NM_013957.5		c.100+4872C>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.100+4872C>T		intron	N/A	ENSP00000384620.2
	NRG1	ENST00000287842.7	TSL:1	c.100+4872C>T		intron	N/A	ENSP00000287842.4
	NRG1	ENST00000356819.7	TSL:1	c.100+4872C>T		intron	N/A	ENSP00000349275.6

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16256 AN: 151910 Hom.: 2075 Cov.: 33

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0888

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.0965

Gnomad FIN AF: 0.0343

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0233

Gnomad OTH AF: 0.0934

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

GnomAD4 genome AF: 0.107 AC: 16287 AN: 152026 Hom.: 2086 Cov.: 33 AF XY: 0.110 AC XY: 8185 AN XY: 74336

African (AFR) AF: 0.221 AC: 9162 AN: 41434

American (AMR) AF: 0.0891 AC: 1360 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 83 AN: 3470

East Asian (EAS) AF: 0.595 AC: 3073 AN: 5164

South Asian (SAS) AF: 0.0960 AC: 463 AN: 4824

European-Finnish (FIN) AF: 0.0343 AC: 363 AN: 10578

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0233 AC: 1582 AN: 67980

Other (OTH) AF: 0.0910 AC: 192 AN: 2110

Alfa AF: 0.0590 Hom.: 4879

Bravo AF: 0.120

Asia WGS AF: 0.256 AC: 890 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.54
PhyloP100		-0.43
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: rs16879552; hg19: chr8-32411216;