chr8-32773810-G-A

Variant names:

• chr8-32773810-G-A
• rs11780123
• NM_013964.5:c.*9408G>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.*9408G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 151,940 control chromosomes in the GnomAD database, including 49,382 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 0.80 (49382 hom., cov: 30)
• Consequence: NRG1 NM_013964.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.808
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_013964.5	c.*9408G>A		3_prime_UTR_variant	Exon 12 of 12	ENST00000405005.8	NP_039258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000405005.8	c.*9408G>A		3_prime_UTR_variant	Exon 12 of 12	1	NM_013964.5	ENSP00000384620.2
NRG1	ENST00000652698.1	c.*9408G>A		3_prime_UTR_variant	Exon 12 of 12			ENSP00000499008.1
NRG1	ENST00000651333.2	c.*10084G>A		3_prime_UTR_variant	Exon 10 of 10			ENSP00000498590.1
NRG1	ENST00000651335.1	c.941+13404G>A		intron_variant	Intron 7 of 7			ENSP00000499047.1

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121056 AN: 151822 Hom.: 49362 Cov.: 30

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.900

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.898

Gnomad OTH AF: 0.840

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

GnomAD4 genome AF: 0.797 AC: 121120 AN: 151940 Hom.: 49382 Cov.: 30 AF XY: 0.793 AC XY: 58926 AN XY: 74262

African (AFR) AF: 0.630 AC: 26072 AN: 41372

American (AMR) AF: 0.786 AC: 12000 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.900 AC: 3122 AN: 3468

East Asian (EAS) AF: 0.655 AC: 3367 AN: 5142

South Asian (SAS) AF: 0.845 AC: 4063 AN: 4806

European-Finnish (FIN) AF: 0.814 AC: 8593 AN: 10562

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.898 AC: 61054 AN: 67998

Other (OTH) AF: 0.842 AC: 1781 AN: 2114

Alfa AF: 0.872 Hom.: 29455

Bravo AF: 0.784

Asia WGS AF: 0.757 AC: 2635 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.36
DANN	Benign	0.60
PhyloP100		-0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11780123; hg19: chr8-32631328;