ENST00000520407.5:c.745+170159A>G

Variant names:

• chr8-31810888-A-G
• rs17603876
• ENST00000520407.5:c.745+170159A>G

Variant summary

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

The ENST00000520407.5(NRG1):​c.745+170159A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0782 in 152,232 control chromosomes in the GnomAD database, including 659 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 0.078 (659 hom., cov: 32)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	NM_001159999.3		c.37+171457A>G		intron	N/A	NP_001153471.1	A0A494C1F5
	NRG1	NM_001159995.3		c.37+171457A>G		intron	N/A	NP_001153467.1	A0A494C1F8
	NRG1	NM_001160001.3		c.37+171457A>G		intron	N/A	NP_001153473.1	Q02297-11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	ENST00000520407.5	TSL:1	c.745+170159A>G		intron	N/A	ENSP00000434640.1	Q02297-9
	NRG1	ENST00000523534.5	TSL:5	c.304+170159A>G		intron	N/A	ENSP00000429067.1	H0YBA3
	NRG1	ENST00000650866.1		c.37+171457A>G		intron	N/A	ENSP00000499045.1	A0A494C1F5

Frequencies

GnomAD3 genomes AF: 0.0783 AC: 11905 AN: 152114 Hom.: 659 Cov.: 32

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.0857

Gnomad AMR AF: 0.0790

Gnomad ASJ AF: 0.0619

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0257

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0908

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

GnomAD4 genome AF: 0.0782 AC: 11901 AN: 152232 Hom.: 659 Cov.: 32 AF XY: 0.0793 AC XY: 5900 AN XY: 74430

African (AFR) AF: 0.0182 AC: 757 AN: 41554

American (AMR) AF: 0.0789 AC: 1207 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0619 AC: 215 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5184

South Asian (SAS) AF: 0.0263 AC: 127 AN: 4828

European-Finnish (FIN) AF: 0.163 AC: 1730 AN: 10590

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7560 AN: 67992

Other (OTH) AF: 0.0894 AC: 189 AN: 2114

Alfa AF: 0.0982 Hom.: 1012

Bravo AF: 0.0686

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.042
DANN	Benign	0.47
PhyloP100		-1.8
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: rs17603876; hg19: chr8-31668404;