ENST00000520407.5:c.745+2019G>A

Variant names:

• chr8-31642748-G-A
• rs1081062
• ENST00000520407.5:c.745+2019G>A

Variant summary

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

The ENST00000520407.5(NRG1):​c.745+2019G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 152,060 control chromosomes in the GnomAD database, including 39,325 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 0.72 (39325 hom., cov: 32)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320
• Publications: 6 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.859 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.37+3317G>A		intron	N/A	NP_001153471.1
	NRG1	NM_001159995.3		c.37+3317G>A		intron	N/A	NP_001153467.1
	NRG1	NM_001160001.3		c.37+3317G>A		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.745+2019G>A		intron	N/A	ENSP00000434640.1
	NRG1	ENST00000523534.5	TSL:5	c.304+2019G>A		intron	N/A	ENSP00000429067.1
	NRG1	ENST00000650866.1		c.37+3317G>A		intron	N/A	ENSP00000499045.1

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109050 AN: 151942 Hom.: 39286 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.743

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

GnomAD4 genome AF: 0.718 AC: 109150 AN: 152060 Hom.: 39325 Cov.: 32 AF XY: 0.713 AC XY: 52971 AN XY: 74318

African (AFR) AF: 0.698 AC: 28939 AN: 41480

American (AMR) AF: 0.701 AC: 10703 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 2526 AN: 3472

East Asian (EAS) AF: 0.880 AC: 4553 AN: 5172

South Asian (SAS) AF: 0.615 AC: 2967 AN: 4824

European-Finnish (FIN) AF: 0.694 AC: 7321 AN: 10544

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.730 AC: 49665 AN: 67990

Other (OTH) AF: 0.746 AC: 1574 AN: 2110

Alfa AF: 0.717 Hom.: 13271

Bravo AF: 0.723

Asia WGS AF: 0.744 AC: 2584 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.64
DANN	Benign	0.58
PhyloP100		-0.32
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: rs1081062; hg19: chr8-31500264;