rs10503926

Positions:

• chr8-32683698-A-C
• chr8-32683698-A-G
• chr8-32683698-A-T

Variant summary

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

The NM_013964.5(NRG1):​c.503-44251A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,758 control chromosomes in the GnomAD database, including 19,594 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 (19594 hom., cov: 29)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.952

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG1	NM_013964.5	c.503-44251A>C		intron_variant		ENST00000405005.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1	ENST00000405005.8	c.503-44251A>C		intron_variant		1	NM_013964.5	A2

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76907 AN: 151640 Hom.: 19579 Cov.: 29

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.507 AC: 76953 AN: 151758 Hom.: 19594 Cov.: 29 AF XY: 0.509 AC XY: 37716 AN XY: 74122

Gnomad4 AFR AF: 0.503

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.488

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.510

Alfa AF: 0.498 Hom.: 30877

Bravo AF: 0.505

Asia WGS AF: 0.491 AC: 1704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	10
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10503926; hg19: chr8-32541216;