rs1481737

Positions:

• chr8-32119713-A-G
• chr8-32119713-A-T

Variant summary

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

The ENST00000520407.5(NRG1):​c.746-476115A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 151,816 control chromosomes in the GnomAD database, including 42,832 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 0.75 (42832 hom., cov: 31)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349

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 (AFR) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG1-IT1	NR_104158.1	n.137-19502A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1-IT1	ENST00000656776.1	n.263-19502A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113280 AN: 151698 Hom.: 42804 Cov.: 31

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.783

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.747 AC: 113356 AN: 151816 Hom.: 42832 Cov.: 31 AF XY: 0.744 AC XY: 55164 AN XY: 74172

Gnomad4 AFR AF: 0.823

Gnomad4 AMR AF: 0.822

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.655

Gnomad4 FIN AF: 0.718

Gnomad4 NFE AF: 0.721

Gnomad4 OTH AF: 0.757

Alfa AF: 0.726 Hom.: 19396

Bravo AF: 0.759

Asia WGS AF: 0.602 AC: 2093 AN: 3476

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	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1481737; hg19: chr8-31977229;