chr8-32683142-G-A

Variant names:

• chr8-32683142-G-A
• rs7829383
• NM_013964.5:c.503-44807G>A

Variant summary

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

The NM_013964.5(NRG1):​c.503-44807G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 152,060 control chromosomes in the GnomAD database, including 35,437 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 0.67 (35437 hom., cov: 33)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013964.5. 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_013964.5	MANE Select	c.503-44807G>A		intron	N/A	NP_039258.1
	NRG1	NM_001322205.2		c.667+34758G>A		intron	N/A	NP_001309134.1
	NRG1	NM_013956.5		c.503-44807G>A		intron	N/A	NP_039250.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	ENST00000405005.8	TSL:1 MANE Select	c.503-44807G>A		intron	N/A	ENSP00000384620.2
	NRG1	ENST00000287842.7	TSL:1	c.503-44807G>A		intron	N/A	ENSP00000287842.4
	NRG1	ENST00000356819.7	TSL:1	c.503-44807G>A		intron	N/A	ENSP00000349275.6

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101750 AN: 151942 Hom.: 35388 Cov.: 33

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.670 AC: 101855 AN: 152060 Hom.: 35437 Cov.: 33 AF XY: 0.665 AC XY: 49427 AN XY: 74322

African (AFR) AF: 0.874 AC: 36273 AN: 41526

American (AMR) AF: 0.598 AC: 9134 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2299 AN: 3470

East Asian (EAS) AF: 0.441 AC: 2271 AN: 5154

South Asian (SAS) AF: 0.554 AC: 2669 AN: 4822

European-Finnish (FIN) AF: 0.615 AC: 6489 AN: 10548

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.597 AC: 40562 AN: 67950

Other (OTH) AF: 0.647 AC: 1369 AN: 2116

Alfa AF: 0.630 Hom.: 5235

Bravo AF: 0.681

Asia WGS AF: 0.542 AC: 1885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.80
DANN	Benign	0.28
PhyloP100		-0.070
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: rs7829383; hg19: chr8-32540660;