ENST00000520407.5:c.746-62787A>G

Variant names:

• chr8-32533041-A-G
• rs10107065
• ENST00000520407.5:c.746-62787A>G

Variant summary

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

The ENST00000520407.5(NRG1):​c.746-62787A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 151,818 control chromosomes in the GnomAD database, including 2,292 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 (2292 hom., cov: 32)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_001159999.3	c.38-62787A>G		intron_variant	Intron 1 of 12		NP_001153471.1
NRG1	NM_001159995.3	c.38-62787A>G		intron_variant	Intron 1 of 11		NP_001153467.1
NRG1	NM_001160001.3	c.38-62787A>G		intron_variant	Intron 1 of 10		NP_001153473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000520407.5	c.746-62787A>G		intron_variant	Intron 1 of 4	1		ENSP00000434640.1
NRG1	ENST00000523534.5	c.305-62787A>G		intron_variant	Intron 1 of 12	5		ENSP00000429067.1
NRG1	ENST00000650866.1	c.38-62787A>G		intron_variant	Intron 1 of 12			ENSP00000499045.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16635 AN: 151700 Hom.: 2279 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0883

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.0989

Gnomad FIN AF: 0.0174

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.0187

Gnomad OTH AF: 0.0930

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

GnomAD4 genome AF: 0.110 AC: 16674 AN: 151818 Hom.: 2292 Cov.: 32 AF XY: 0.112 AC XY: 8278 AN XY: 74182

African (AFR) AF: 0.245 AC: 10159 AN: 41422

American (AMR) AF: 0.0886 AC: 1351 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 86 AN: 3466

East Asian (EAS) AF: 0.571 AC: 2955 AN: 5174

South Asian (SAS) AF: 0.0983 AC: 474 AN: 4820

European-Finnish (FIN) AF: 0.0174 AC: 184 AN: 10578

Middle Eastern (MID) AF: 0.0240 AC: 7 AN: 292

European-Non Finnish (NFE) AF: 0.0187 AC: 1267 AN: 67802

Other (OTH) AF: 0.0906 AC: 191 AN: 2108

Alfa AF: 0.0465 Hom.: 238

Bravo AF: 0.125

Asia WGS AF: 0.253 AC: 876 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.3
DANN	Benign	0.74
PhyloP100		1.7
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: rs10107065; hg19: chr8-32390558;