chr8-31948532-T-C

Variant names:

• chr8-31948532-T-C
• rs383632
• ENST00000520407.5:c.745+307803T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000520407.5(NRG1):​c.745+307803T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 152,134 control chromosomes in the GnomAD database, including 62,306 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 0.90 (62306 hom., cov: 31)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• schizophrenia 6

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000520407.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	NM_001159999.3		c.37+309101T>C		intron	N/A	NP_001153471.1
	NRG1	NM_001159995.3		c.37+309101T>C		intron	N/A	NP_001153467.1
	NRG1	NM_001160001.3		c.37+309101T>C		intron	N/A	NP_001153473.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	ENST00000520407.5	TSL:1	c.745+307803T>C		intron	N/A	ENSP00000434640.1
	NRG1	ENST00000523534.5	TSL:5	c.304+307803T>C		intron	N/A	ENSP00000429067.1
	NRG1	ENST00000650866.1		c.37+309101T>C		intron	N/A	ENSP00000499045.1

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136677 AN: 152016 Hom.: 62237 Cov.: 31

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.861

Gnomad AMR AF: 0.877

Gnomad ASJ AF: 0.889

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.909

Gnomad OTH AF: 0.904

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

GnomAD4 genome AF: 0.899 AC: 136807 AN: 152134 Hom.: 62306 Cov.: 31 AF XY: 0.894 AC XY: 66439 AN XY: 74340

African (AFR) AF: 0.967 AC: 40168 AN: 41520

American (AMR) AF: 0.877 AC: 13416 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.889 AC: 3085 AN: 3472

East Asian (EAS) AF: 0.395 AC: 2024 AN: 5130

South Asian (SAS) AF: 0.835 AC: 4012 AN: 4804

European-Finnish (FIN) AF: 0.879 AC: 9286 AN: 10570

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.909 AC: 61853 AN: 68028

Other (OTH) AF: 0.904 AC: 1910 AN: 2112

Alfa AF: 0.906 Hom.: 27975

Bravo AF: 0.899

Asia WGS AF: 0.689 AC: 2396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.70
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs383632; hg19: chr8-31806048;