rs11989919

Variant names:

• chr8-32645107-T-C
• rs11989919
• NM_013964.5:c.502+28222T>C

Variant summary

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

The NM_013964.5(NRG1):​c.502+28222T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,214 control chromosomes in the GnomAD database, including 1,934 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 0.11 (1934 hom., cov: 32)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.399
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_013964.5	c.502+28222T>C		intron_variant	Intron 5 of 11	ENST00000405005.8	NP_039258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000405005.8	c.502+28222T>C		intron_variant	Intron 5 of 11	1	NM_013964.5	ENSP00000384620.2

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15979 AN: 152096 Hom.: 1934 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0342

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0155

Gnomad OTH AF: 0.0931

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

GnomAD4 genome AF: 0.105 AC: 15986 AN: 152214 Hom.: 1934 Cov.: 32 AF XY: 0.109 AC XY: 8099 AN XY: 74424

African (AFR) AF: 0.206 AC: 8549 AN: 41514

American (AMR) AF: 0.157 AC: 2399 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 71 AN: 3468

East Asian (EAS) AF: 0.544 AC: 2809 AN: 5164

South Asian (SAS) AF: 0.112 AC: 541 AN: 4822

European-Finnish (FIN) AF: 0.0342 AC: 363 AN: 10618

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0155 AC: 1053 AN: 68020

Other (OTH) AF: 0.0917 AC: 194 AN: 2116

Alfa AF: 0.0486 Hom.: 3337

Bravo AF: 0.123

Asia WGS AF: 0.251 AC: 874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.5
DANN	Benign	0.59
PhyloP100		-0.40
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: rs11989919; hg19: chr8-32502626;