rs2919390

chr8-32669436-A-Cchr8-32669436-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.502+52551A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 151,928 control chromosomes in the GnomAD database, including 14,692 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 0.43 (14692 hom., cov: 32)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG1	NM_013964.5	c.502+52551A>C		intron_variant		ENST00000405005.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1	ENST00000405005.8	c.502+52551A>C		intron_variant		1	NM_013964.5	A2

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65145 AN: 151812 Hom.: 14673 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.429 AC: 65211 AN: 151928 Hom.: 14692 Cov.: 32 AF XY: 0.436 AC XY: 32399 AN XY: 74264

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.846

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.402

Alfa AF: 0.400 Hom.: 17639

Bravo AF: 0.435

Asia WGS AF: 0.590 AC: 2047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	5.1
Dann	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2919390; hg19: chr8-32526955;