chr8-32376597-G-A

Position:

• chr8-32376597-G-A

Variant summary

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

The NM_001159999.3(NRG1):​c.38-219231G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 152,152 control chromosomes in the GnomAD database, including 51,627 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 (51627 hom., cov: 32)
• Consequence: NRG1 NM_001159999.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRG1	NM_001159999.3	c.38-219231G>A		intron_variant			NP_001153471.1
NRG1	NM_001159995.3	c.38-219231G>A		intron_variant			NP_001153467.1
NRG1	NM_001160001.3	c.38-219231G>A		intron_variant			NP_001153473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000520407.5	c.746-219231G>A		intron_variant		1		ENSP00000434640.1
NRG1	ENST00000523534.5	c.305-219231G>A		intron_variant		5		ENSP00000429067.1
NRG1	ENST00000650866.1	c.38-219231G>A		intron_variant				ENSP00000499045.1

Frequencies

GnomAD3 genomes AF: 0.823 AC: 125105 AN: 152034 Hom.: 51587 Cov.: 32

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.839

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

GnomAD4 genome AF: 0.823 AC: 125202 AN: 152152 Hom.: 51627 Cov.: 32 AF XY: 0.821 AC XY: 61044 AN XY: 74388

Gnomad4 AFR AF: 0.800

Gnomad4 AMR AF: 0.841

Gnomad4 ASJ AF: 0.933

Gnomad4 EAS AF: 0.837

Gnomad4 SAS AF: 0.804

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.837

Gnomad4 OTH AF: 0.837

Alfa AF: 0.837 Hom.: 50481

Bravo AF: 0.829

Asia WGS AF: 0.808 AC: 2811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.24

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10503913; hg19: chr8-32234113; COSMIC: COSV73066203;