8-32532544-G-T

Variant names:

• chr8-32532544-G-T
• rs10088313
• ENST00000520407.5:c.746-63284G>T

Variant summary

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

The ENST00000520407.5(NRG1):​c.746-63284G>T 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 151,976 control chromosomes in the GnomAD database, including 2,287 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 (2287 hom., cov: 32)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.429
• Publications: 2 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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.554 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.38-63284G>T		intron	N/A	NP_001153471.1
	NRG1	NM_001159995.3		c.38-63284G>T		intron	N/A	NP_001153467.1
	NRG1	NM_001160001.3		c.38-63284G>T		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.746-63284G>T		intron	N/A	ENSP00000434640.1
	NRG1	ENST00000523534.5	TSL:5	c.305-63284G>T		intron	N/A	ENSP00000429067.1
	NRG1	ENST00000650866.1		c.38-63284G>T		intron	N/A	ENSP00000499045.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16646 AN: 151856 Hom.: 2274 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0885

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.0988

Gnomad FIN AF: 0.0173

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0187

Gnomad OTH AF: 0.0929

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

GnomAD4 genome AF: 0.110 AC: 16685 AN: 151976 Hom.: 2287 Cov.: 32 AF XY: 0.112 AC XY: 8286 AN XY: 74288

African (AFR) AF: 0.245 AC: 10174 AN: 41464

American (AMR) AF: 0.0888 AC: 1357 AN: 15278

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

East Asian (EAS) AF: 0.571 AC: 2945 AN: 5154

South Asian (SAS) AF: 0.0982 AC: 473 AN: 4818

European-Finnish (FIN) AF: 0.0173 AC: 183 AN: 10572

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

European-Non Finnish (NFE) AF: 0.0187 AC: 1269 AN: 67910

Other (OTH) AF: 0.0905 AC: 191 AN: 2110

Alfa AF: 0.0505 Hom.: 143

Bravo AF: 0.125

Asia WGS AF: 0.252 AC: 874 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.69
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: rs10088313; hg19: chr8-32390061;