rs6982890

chr8-32757580-C-T

Variant summary

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

The NM_013964.5(NRG1):c.930+1051C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,122 control chromosomes in the GnomAD database, including 3,203 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 0.20 (3203 hom., cov: 32)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG1	NM_013964.5	c.930+1051C>T		intron_variant		ENST00000405005.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1	ENST00000405005.8	c.930+1051C>T		intron_variant		1	NM_013964.5	A2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29840 AN: 152004 Hom.: 3186 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.196 AC: 29877 AN: 152122 Hom.: 3203 Cov.: 32 AF XY: 0.189 AC XY: 14086 AN XY: 74370

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.225

Alfa AF: 0.234 Hom.: 6275

Bravo AF: 0.196

Asia WGS AF: 0.248 AC: 862 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.8
Dann	Benign	0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6982890; hg19: chr8-32615098;