rs10503899

chr8-32089718-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+448989A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,148 control chromosomes in the GnomAD database, including 10,378 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 0.33 (10378 hom., cov: 32)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.860

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG1-IT1	NR_104158.1	n.137-49497A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1-IT1	ENST00000656776.1	n.263-49497A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50178 AN: 152028 Hom.: 10373 Cov.: 32

Gnomad AFR AF: 0.0883

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.330 AC: 50190 AN: 152148 Hom.: 10378 Cov.: 32 AF XY: 0.330 AC XY: 24517 AN XY: 74368

Gnomad4 AFR AF: 0.0881

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.343

Alfa AF: 0.429 Hom.: 19226

Bravo AF: 0.312

Asia WGS AF: 0.267 AC: 926 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.6
Dann	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10503899; hg19: chr8-31947234;