8-32282136-G-C

Variant names:

• chr8-32282136-G-C
• rs1487141
• ENST00000520407.5:c.746-313692G>C

Variant summary

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

The ENST00000520407.5(NRG1):​c.746-313692G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,058 control chromosomes in the GnomAD database, including 5,272 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 0.24 (5272 hom., cov: 32)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.535
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000520407.5. 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_001159999.3		c.38-313692G>C		intron	N/A	NP_001153471.1
	NRG1	NM_001159995.3		c.38-313692G>C		intron	N/A	NP_001153467.1
	NRG1	NM_001160001.3		c.38-313692G>C		intron	N/A	NP_001153473.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	ENST00000520407.5	TSL:1	c.746-313692G>C		intron	N/A	ENSP00000434640.1
	NRG1	ENST00000523534.5	TSL:5	c.305-313692G>C		intron	N/A	ENSP00000429067.1
	NRG1	ENST00000650866.1		c.38-313692G>C		intron	N/A	ENSP00000499045.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36518 AN: 151940 Hom.: 5262 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.240 AC: 36569 AN: 152058 Hom.: 5272 Cov.: 32 AF XY: 0.246 AC XY: 18247 AN XY: 74316

African (AFR) AF: 0.409 AC: 16971 AN: 41466

American (AMR) AF: 0.193 AC: 2956 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 729 AN: 3468

East Asian (EAS) AF: 0.198 AC: 1020 AN: 5152

South Asian (SAS) AF: 0.152 AC: 732 AN: 4818

European-Finnish (FIN) AF: 0.299 AC: 3157 AN: 10572

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.152 AC: 10368 AN: 67990

Other (OTH) AF: 0.217 AC: 459 AN: 2112

Alfa AF: 0.102 Hom.: 165

Bravo AF: 0.242

Asia WGS AF: 0.198 AC: 689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.6
DANN	Benign	0.65
PhyloP100		0.54
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: rs1487141; hg19: chr8-32139652;