8-32548461-T-C

Position:

• chr8-32548461-T-C

Variant summary

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

The NM_013964.5(NRG1):​c.-266T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 1,170,154 control chromosomes in the GnomAD database, including 356,018 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 0.78 (46930 hom., cov: 32)
  • Exomes 𝑓: 0.78 (309088 hom.)
• Consequence: NRG1 NM_013964.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRG1	NM_013964.5	c.-266T>C		5_prime_UTR_variant	1/12	ENST00000405005.8	NP_039258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000405005.8	c.-266T>C		5_prime_UTR_variant	1/12	1	NM_013964.5	ENSP00000384620	A2

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119071 AN: 151714 Hom.: 46892 Cov.: 32

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.769

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.794

GnomAD4 exome AF: 0.779 AC: 792843 AN: 1018332 Hom.: 309088 Cov.: 70 AF XY: 0.778 AC XY: 372559 AN XY: 478786

Gnomad4 AFR exome AF: 0.754

Gnomad4 AMR exome AF: 0.864

Gnomad4 ASJ exome AF: 0.760

Gnomad4 EAS exome AF: 0.866

Gnomad4 SAS exome AF: 0.657

Gnomad4 FIN exome AF: 0.807

Gnomad4 NFE exome AF: 0.780

Gnomad4 OTH exome AF: 0.769

GnomAD4 genome AF: 0.785 AC: 119159 AN: 151822 Hom.: 46930 Cov.: 32 AF XY: 0.785 AC XY: 58252 AN XY: 74182

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.866

Gnomad4 ASJ AF: 0.769

Gnomad4 EAS AF: 0.799

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.824

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.790

Alfa AF: 0.729 Hom.: 2219

Bravo AF: 0.791

Asia WGS AF: 0.710 AC: 2448 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7820838; hg19: chr8-32405979;