8-32743286-A-G

Position:

• chr8-32743286-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_013964.5(NRG1):​c.700+1211A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0254 in 918,786 control chromosomes in the GnomAD database, including 365 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 0.023 (68 hom., cov: 32)
  • Exomes 𝑓: 0.026 (297 hom.)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.17

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).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0229 (3492/152206) while in subpopulation NFE AF= 0.0299 (2032/67996). AF 95% confidence interval is 0.0288. There are 68 homozygotes in gnomad4. There are 1817 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3492 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG1	NM_013964.5	c.700+1211A>G		intron_variant		ENST00000405005.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1	ENST00000405005.8	c.700+1211A>G		intron_variant		1	NM_013964.5	A2

Frequencies

GnomAD3 genomes AF: 0.0230 AC: 3492 AN: 152090 Hom.: 68 Cov.: 32

Gnomad AFR AF: 0.00473

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0205

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00663

Gnomad FIN AF: 0.0740

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0299

Gnomad OTH AF: 0.0229

GnomAD4 exome AF: 0.0259 AC: 19841 AN: 766580 Hom.: 297 Cov.: 11 AF XY: 0.0258 AC XY: 9161 AN XY: 355540

Gnomad4 AFR exome AF: 0.00299

Gnomad4 AMR exome AF: 0.0136

Gnomad4 ASJ exome AF: 0.0262

Gnomad4 EAS exome AF: 0.000307

Gnomad4 SAS exome AF: 0.00883

Gnomad4 FIN exome AF: 0.0504

Gnomad4 NFE exome AF: 0.0270

Gnomad4 OTH exome AF: 0.0224

GnomAD4 genome AF: 0.0229 AC: 3492 AN: 152206 Hom.: 68 Cov.: 32 AF XY: 0.0244 AC XY: 1817 AN XY: 74396

Gnomad4 AFR AF: 0.00471

Gnomad4 AMR AF: 0.0206

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00684

Gnomad4 FIN AF: 0.0740

Gnomad4 NFE AF: 0.0299

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0278 Hom.: 6

Bravo AF: 0.0179

Asia WGS AF: 0.00231 AC: 8 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.0
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs79916768; hg19: chr8-32600804;