chr8-32125908-G-T

Position:

• chr8-32125908-G-T

Variant summary

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

The ENST00000520407.5(NRG1):​c.746-469920G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 151,800 control chromosomes in the GnomAD database, including 34,178 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 0.66 (34178 hom., cov: 32)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303

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-IT1 (HGNC:43633): (NRG1 intronic transcript 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG1-IT1	NR_104158.1	n.137-13307G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1-IT1	ENST00000656776.1	n.263-13307G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99791 AN: 151682 Hom.: 34127 Cov.: 32

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.658 AC: 99907 AN: 151800 Hom.: 34178 Cov.: 32 AF XY: 0.658 AC XY: 48848 AN XY: 74198

Gnomad4 AFR AF: 0.852

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.603

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.624

Alfa AF: 0.592 Hom.: 10636

Bravo AF: 0.671

Asia WGS AF: 0.592 AC: 2061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.20

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2346771; hg19: chr8-31983424;