rs16879576

Variant names:

• chr8-32583717-C-A
• rs16879576
• NM_013964.5:c.101-12111C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-32583717-C-A
• chr8-32583717-C-G
• chr8-32583717-C-T

Variant summary

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

The NM_013964.5(NRG1):​c.101-12111C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0925 in 152,216 control chromosomes in the GnomAD database, including 1,774 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 0.093 (1774 hom., cov: 33)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• 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 (EAS) allele frequency at 95% confidence interval = 0.564 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	NM_013964.5	MANE Select	c.101-12111C>A		intron	N/A	NP_039258.1	Q02297-1
	NRG1	NM_013956.5		c.101-12111C>A		intron	N/A	NP_039250.2	Q02297-6
	NRG1	NM_013957.5		c.101-12111C>A		intron	N/A	NP_039251.2	Q02297-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	ENST00000405005.8	TSL:1 MANE Select	c.101-12111C>A		intron	N/A	ENSP00000384620.2	Q02297-1
	NRG1	ENST00000287842.7	TSL:1	c.101-12111C>A		intron	N/A	ENSP00000287842.4	Q02297-6
	NRG1	ENST00000356819.7	TSL:1	c.101-12111C>A		intron	N/A	ENSP00000349275.6	Q02297-7

Frequencies

GnomAD3 genomes AF: 0.0925 AC: 14062 AN: 152100 Hom.: 1769 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0814

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.0601

Gnomad FIN AF: 0.0166

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0170

Gnomad OTH AF: 0.0799

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

GnomAD4 genome AF: 0.0925 AC: 14080 AN: 152216 Hom.: 1774 Cov.: 33 AF XY: 0.0951 AC XY: 7075 AN XY: 74422

African (AFR) AF: 0.193 AC: 7996 AN: 41490

American (AMR) AF: 0.0814 AC: 1245 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3472

East Asian (EAS) AF: 0.581 AC: 2999 AN: 5162

South Asian (SAS) AF: 0.0594 AC: 287 AN: 4834

European-Finnish (FIN) AF: 0.0166 AC: 176 AN: 10620

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0170 AC: 1154 AN: 68026

Other (OTH) AF: 0.0777 AC: 164 AN: 2110

Alfa AF: 0.0587 Hom.: 2008

Bravo AF: 0.107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.2
DANN	Benign	0.54
PhyloP100		0.055
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: rs16879576; hg19: chr8-32441235;