8-32030978-A-G

Variant names:

• chr8-32030978-A-G
• rs7827456
• ENST00000520407.5:c.745+390249A>G

Variant summary

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

The NM_001159999.3(NRG1):​c.37+391547A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 152,046 control chromosomes in the GnomAD database, including 25,629 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 0.53 (25629 hom., cov: 31)
• Consequence: NRG1 NM_001159999.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486
• 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-IT1 (HGNC:43633): (NRG1 intronic transcript 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.709 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.37+391547A>G		intron	N/A	NP_001153471.1	A0A494C1F5
	NRG1	NM_001159995.3		c.37+391547A>G		intron	N/A	NP_001153467.1	A0A494C1F8
	NRG1	NM_001160001.3		c.37+391547A>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+390249A>G		intron	N/A	ENSP00000434640.1	Q02297-9
	NRG1-IT1	ENST00000521463.6	TSL:1	n.253+1493A>G		intron	N/A
	NRG1	ENST00000523534.5	TSL:5	c.304+390249A>G		intron	N/A	ENSP00000429067.1	H0YBA3

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80217 AN: 151928 Hom.: 25619 Cov.: 31

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.528 AC: 80229 AN: 152046 Hom.: 25629 Cov.: 31 AF XY: 0.528 AC XY: 39207 AN XY: 74300

African (AFR) AF: 0.168 AC: 6977 AN: 41480

American (AMR) AF: 0.568 AC: 8690 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2156 AN: 3472

East Asian (EAS) AF: 0.278 AC: 1435 AN: 5156

South Asian (SAS) AF: 0.590 AC: 2839 AN: 4810

European-Finnish (FIN) AF: 0.713 AC: 7533 AN: 10564

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48567 AN: 67952

Other (OTH) AF: 0.558 AC: 1179 AN: 2114

Alfa AF: 0.651 Hom.: 55503

Bravo AF: 0.497

Asia WGS AF: 0.445 AC: 1547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.38
PhyloP100		-0.49
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: rs7827456; hg19: chr8-31888494;