rs16879425

Positions:

• chr8-32449690-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000520407.5(NRG1):​c.746-146138A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,254 control chromosomes in the GnomAD database, including 1,870 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 0.12 (1870 hom., cov: 32)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRG1	NM_001159995.3	c.38-146138A>C		intron_variant			NP_001153467.1
NRG1	NM_001159999.3	c.38-146138A>C		intron_variant			NP_001153471.1
NRG1	NM_001160001.3	c.38-146138A>C		intron_variant			NP_001153473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000520407.5	c.746-146138A>C		intron_variant		1		ENSP00000434640
NRG1	ENST00000519301.6	c.38-146138A>C		intron_variant		5		ENSP00000429582
NRG1	ENST00000523534.5	c.305-146138A>C		intron_variant		5		ENSP00000429067

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18480 AN: 152136 Hom.: 1868 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0812

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0979

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.122 AC: 18500 AN: 152254 Hom.: 1870 Cov.: 32 AF XY: 0.126 AC XY: 9366 AN XY: 74444

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.0942

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.0812

Gnomad4 NFE AF: 0.0979

Gnomad4 OTH AF: 0.116

Alfa AF: 0.104 Hom.: 181

Bravo AF: 0.129

Asia WGS AF: 0.276 AC: 960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16879425; hg19: chr8-32307206;