8-32562829-C-A

Variant names:

• chr8-32562829-C-A
• rs4316112
• NM_013964.5:c.100+14003C>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.100+14003C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,102 control chromosomes in the GnomAD database, including 3,873 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 0.20 (3873 hom., cov: 32)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_013964.5	c.100+14003C>A		intron_variant	Intron 1 of 11	ENST00000405005.8	NP_039258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000405005.8	c.100+14003C>A		intron_variant	Intron 1 of 11	1	NM_013964.5	ENSP00000384620.2

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30377 AN: 151984 Hom.: 3867 Cov.: 32

Gnomad AFR AF: 0.0542

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.0543

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.200 AC: 30396 AN: 152102 Hom.: 3873 Cov.: 32 AF XY: 0.204 AC XY: 15159 AN XY: 74338

African (AFR) AF: 0.0542 AC: 2249 AN: 41524

American (AMR) AF: 0.330 AC: 5047 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 742 AN: 3464

East Asian (EAS) AF: 0.0540 AC: 280 AN: 5182

South Asian (SAS) AF: 0.216 AC: 1043 AN: 4818

European-Finnish (FIN) AF: 0.308 AC: 3247 AN: 10546

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17149 AN: 67982

Other (OTH) AF: 0.208 AC: 439 AN: 2106

Alfa AF: 0.176 Hom.: 601

Bravo AF: 0.197

Asia WGS AF: 0.152 AC: 530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.14
DANN	Benign	0.35
PhyloP100		-0.66
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: rs4316112; hg19: chr8-32420347;