rs10503927

Variant names:

• chr8-32685712-C-T
• rs10503927
• NM_013964.5:c.503-42237C>T

Variant summary

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

The NM_013964.5(NRG1):​c.503-42237C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 151,970 control chromosomes in the GnomAD database, including 19,483 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 0.51 (19483 hom., cov: 33)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.742

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=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_013964.5	c.503-42237C>T		intron_variant	Intron 5 of 11	ENST00000405005.8	NP_039258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000405005.8	c.503-42237C>T		intron_variant	Intron 5 of 11	1	NM_013964.5	ENSP00000384620.2

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76735 AN: 151852 Hom.: 19470 Cov.: 33

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.494

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.505 AC: 76778 AN: 151970 Hom.: 19483 Cov.: 33 AF XY: 0.507 AC XY: 37653 AN XY: 74264

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.506

Gnomad4 OTH AF: 0.509

Alfa AF: 0.508 Hom.: 8906

Bravo AF: 0.503

Asia WGS AF: 0.482 AC: 1675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10503927; hg19: chr8-32543230;