chr10-82554641-G-C

Variant names:

• chr10-82554641-G-C
• rs677221
• NM_001010848.4:c.954-183936G>C

Variant summary

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

The NM_001010848.4(NRG3):​c.954-183936G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 151,916 control chromosomes in the GnomAD database, including 21,428 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 0.49 (21428 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143
• Publications: 5 publications found

Genes affected

NRG3 (HGNC:7999): (neuregulin 3) This gene is a member of the neuregulin gene family. This gene family encodes ligands for the transmembrane tyrosine kinase receptors ERBB3 and ERBB4 - members of the epidermal growth factor receptor family. Ligand binding activates intracellular signaling cascades and the induction of cellular responses including proliferation, migration, differentiation, and survival or apoptosis. This gene encodes neuregulin 3 (NRG3). NRG3 has been shown to activate the tyrosine phosphorylation of its cognate receptor, ERBB4, and is thought to influence neuroblast proliferation, migration and differentiation by signalling through ERBB4. NRG3 also promotes mammary differentiation during embryogenesis. Linkage studies have implicated this gene as a susceptibility locus for schizophrenia and schizoaffective disorder. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described but their biological validity has not been verified.[provided by RefSeq, Sep 2009]

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 (AFR) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010848.4. 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
	NRG3	NM_001010848.4	MANE Select	c.954-183936G>C		intron	N/A	NP_001010848.2
	NRG3	NM_001370084.1		c.954-183936G>C		intron	N/A	NP_001357013.1
	NRG3	NM_001370081.1		c.954-183936G>C		intron	N/A	NP_001357010.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG3	ENST00000372141.7	TSL:1 MANE Select	c.954-183936G>C		intron	N/A	ENSP00000361214.2
	NRG3	ENST00000404547.5	TSL:1	c.954-183936G>C		intron	N/A	ENSP00000384796.1
	NRG3	ENST00000556918.5	TSL:1	c.444-183936G>C		intron	N/A	ENSP00000451376.1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74262 AN: 151798 Hom.: 21372 Cov.: 32

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.490 AC: 74376 AN: 151916 Hom.: 21428 Cov.: 32 AF XY: 0.485 AC XY: 36028 AN XY: 74210

African (AFR) AF: 0.805 AC: 33353 AN: 41432

American (AMR) AF: 0.495 AC: 7536 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1152 AN: 3468

East Asian (EAS) AF: 0.584 AC: 3007 AN: 5146

South Asian (SAS) AF: 0.290 AC: 1396 AN: 4816

European-Finnish (FIN) AF: 0.301 AC: 3178 AN: 10562

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.343 AC: 23332 AN: 67946

Other (OTH) AF: 0.476 AC: 1006 AN: 2112

Alfa AF: 0.423 Hom.: 1965

Bravo AF: 0.522

Asia WGS AF: 0.475 AC: 1652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.2
DANN	Benign	0.65
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs677221; hg19: chr10-84314397;