rs10503898

Positions:

• chr8-32086200-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+445471A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0602 in 152,280 control chromosomes in the GnomAD database, including 813 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 0.060 (813 hom., cov: 33)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG1-IT1	NR_104158.1	n.137-53015A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1-IT1	ENST00000656776.1	n.263-53015A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0601 AC: 9151 AN: 152162 Hom.: 813 Cov.: 33

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0238

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.0779

Gnomad SAS AF: 0.0633

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000867

Gnomad OTH AF: 0.0550

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

GnomAD4 genome AF: 0.0602 AC: 9167 AN: 152280 Hom.: 813 Cov.: 33 AF XY: 0.0590 AC XY: 4391 AN XY: 74464

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.0238

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.0777

Gnomad4 SAS AF: 0.0631

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000867

Gnomad4 OTH AF: 0.0549

Alfa AF: 0.0221 Hom.: 55

Bravo AF: 0.0668

Asia WGS AF: 0.0880 AC: 304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10503898; hg19: chr8-31943716;