8-32594380-A-G

Position:

• chr8-32594380-A-G

Variant summary

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

The NM_013964.5(NRG1):​c.101-1448A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 152,092 control chromosomes in the GnomAD database, including 52,507 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 0.82 (52507 hom., cov: 32)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

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]

NRG1 (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRG1	NM_013964.5	c.101-1448A>G		intron_variant		ENST00000405005.8	NP_039258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000405005.8	c.101-1448A>G		intron_variant		1	NM_013964.5	ENSP00000384620.2

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124411 AN: 151974 Hom.: 52483 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.929

Gnomad EAS AF: 0.938

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.849

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

GnomAD4 genome AF: 0.819 AC: 124489 AN: 152092 Hom.: 52507 Cov.: 32 AF XY: 0.820 AC XY: 60956 AN XY: 74368

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.851

Gnomad4 ASJ AF: 0.929

Gnomad4 EAS AF: 0.938

Gnomad4 SAS AF: 0.944

Gnomad4 FIN AF: 0.887

Gnomad4 NFE AF: 0.915

Gnomad4 OTH AF: 0.852

Alfa AF: 0.898 Hom.: 90171

Bravo AF: 0.804

Asia WGS AF: 0.931 AC: 3240 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	3.7
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: rs4602844; hg19: chr8-32451898;