chr8-32488779-G-A

Variant names:

• chr8-32488779-G-A
• rs10097555
• ENST00000520407.5:c.746-107049G>A

Variant summary

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

The NM_001159999.3(NRG1):​c.38-107049G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 151,966 control chromosomes in the GnomAD database, including 29,764 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 0.62 (29764 hom., cov: 31)
• Consequence: NRG1 NM_001159999.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• 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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159999.3. 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.38-107049G>A		intron	N/A	NP_001153471.1	A0A494C1F5
	NRG1	NM_001159995.3		c.38-107049G>A		intron	N/A	NP_001153467.1	A0A494C1F8
	NRG1	NM_001160001.3		c.38-107049G>A		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.746-107049G>A		intron	N/A	ENSP00000434640.1	Q02297-9
	NRG1	ENST00000523534.5	TSL:5	c.305-107049G>A		intron	N/A	ENSP00000429067.1	H0YBA3
	NRG1	ENST00000650866.1		c.38-107049G>A		intron	N/A	ENSP00000499045.1	A0A494C1F5

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94664 AN: 151850 Hom.: 29745 Cov.: 31

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.623 AC: 94722 AN: 151966 Hom.: 29764 Cov.: 31 AF XY: 0.623 AC XY: 46285 AN XY: 74248

African (AFR) AF: 0.630 AC: 26107 AN: 41440

American (AMR) AF: 0.585 AC: 8932 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 2139 AN: 3468

East Asian (EAS) AF: 0.788 AC: 4064 AN: 5158

South Asian (SAS) AF: 0.582 AC: 2796 AN: 4804

European-Finnish (FIN) AF: 0.613 AC: 6463 AN: 10538

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.618 AC: 42039 AN: 67976

Other (OTH) AF: 0.618 AC: 1302 AN: 2106

Alfa AF: 0.612 Hom.: 6938

Bravo AF: 0.620

Asia WGS AF: 0.625 AC: 2172 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.5
DANN	Benign	0.79
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: rs10097555; hg19: chr8-32346295; COSMIC: COSV73061988;