rs2919375

Positions:

• chr8-32719327-G-A
• chr8-32719327-G-T

Variant summary

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

The NM_013964.5(NRG1):​c.503-8622G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 151,880 control chromosomes in the GnomAD database, including 44,922 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 0.77 (44922 hom., cov: 31)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG1	NM_013964.5	c.503-8622G>A		intron_variant		ENST00000405005.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1	ENST00000405005.8	c.503-8622G>A		intron_variant		1	NM_013964.5	A2

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116137 AN: 151764 Hom.: 44874 Cov.: 31

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.785

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

GnomAD4 genome AF: 0.765 AC: 116251 AN: 151880 Hom.: 44922 Cov.: 31 AF XY: 0.760 AC XY: 56398 AN XY: 74202

Gnomad4 AFR AF: 0.841

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.729

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.747

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.771

Gnomad4 OTH AF: 0.787

Alfa AF: 0.765 Hom.: 16219

Bravo AF: 0.757

Asia WGS AF: 0.705 AC: 2444 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.37
DANN	Benign	0.29

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2919375; hg19: chr8-32576845;