8-32685523-A-T

Position:

• chr8-32685523-A-T

Variant summary

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

The NM_013964.5(NRG1):​c.503-42426A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,980 control chromosomes in the GnomAD database, including 19,544 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 0.51 (19544 hom., cov: 32)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG1	NM_013964.5	c.503-42426A>T		intron_variant		ENST00000405005.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1	ENST00000405005.8	c.503-42426A>T		intron_variant		1	NM_013964.5	A2

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76881 AN: 151860 Hom.: 19529 Cov.: 32

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.506 AC: 76927 AN: 151980 Hom.: 19544 Cov.: 32 AF XY: 0.508 AC XY: 37729 AN XY: 74272

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.509

Alfa AF: 0.495 Hom.: 2215

Bravo AF: 0.504

Asia WGS AF: 0.484 AC: 1682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7823899; hg19: chr8-32543041;