8-32030978-A-G

Variant summary

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

The ENST00000520407.5(NRG1):c.745+390249A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 152,046 control chromosomes in the GnomAD database, including 25,629 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 0.53 (25629 hom., cov: 31)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486

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-IT1 (HGNC:43633): (NRG1 intronic transcript 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG1-IT1	NR_104158.1	n.136+1493A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1-IT1	ENST00000656776.1	n.262+1493A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80217 AN: 151928 Hom.: 25619 Cov.: 31

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.528 AC: 80229 AN: 152046 Hom.: 25629 Cov.: 31 AF XY: 0.528 AC XY: 39207 AN XY: 74300

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.713

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.558

Alfa AF: 0.669 Hom.: 45084

Bravo AF: 0.497

Asia WGS AF: 0.445 AC: 1547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.1
Dann	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7827456; hg19: chr8-31888494;