rs16879814

Positions:

• chr8-32716065-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.503-11884T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,060 control chromosomes in the GnomAD database, including 8,070 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 0.32 (8070 hom., cov: 32)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRG1	NM_013964.5	c.503-11884T>C		intron_variant		ENST00000405005.8	NP_039258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000405005.8	c.503-11884T>C		intron_variant		1	NM_013964.5	ENSP00000384620	A2

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48271 AN: 151942 Hom.: 8069 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.0889

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.318 AC: 48284 AN: 152060 Hom.: 8070 Cov.: 32 AF XY: 0.319 AC XY: 23719 AN XY: 74334

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.0891

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.300

Alfa AF: 0.343 Hom.: 12443

Bravo AF: 0.305

Asia WGS AF: 0.182 AC: 632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16879814; hg19: chr8-32573583;