8-32571171-A-G

Position:

• chr8-32571171-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.100+22345A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,104 control chromosomes in the GnomAD database, including 7,565 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 0.29 (7565 hom., cov: 32)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.960

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRG1	NM_013964.5	c.100+22345A>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.100+22345A>G		intron_variant		1	NM_013964.5	ENSP00000384620.2

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43801 AN: 151986 Hom.: 7568 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.288 AC: 43811 AN: 152104 Hom.: 7565 Cov.: 32 AF XY: 0.291 AC XY: 21651 AN XY: 74342

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.794

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.292

Alfa AF: 0.311 Hom.: 4097

Bravo AF: 0.282

Asia WGS AF: 0.548 AC: 1906 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10503920; hg19: chr8-32428689;