rs7826312

Variant names:

• chr8-32542597-T-C
• rs7826312
• ENST00000520407.5:c.746-53231T>C

Variant summary

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

The ENST00000520407.5(NRG1):​c.746-53231T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,928 control chromosomes in the GnomAD database, including 24,407 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 0.56 (24407 hom., cov: 32)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.428
• Publications: 20 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_001159999.3	c.38-53231T>C		intron_variant	Intron 1 of 12		NP_001153471.1
NRG1	NM_001159995.3	c.38-53231T>C		intron_variant	Intron 1 of 11		NP_001153467.1
NRG1	NM_001160001.3	c.38-53231T>C		intron_variant	Intron 1 of 10		NP_001153473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000520407.5	c.746-53231T>C		intron_variant	Intron 1 of 4	1		ENSP00000434640.1
NRG1	ENST00000523534.5	c.305-53231T>C		intron_variant	Intron 1 of 12	5		ENSP00000429067.1
NRG1	ENST00000650866.1	c.38-53231T>C		intron_variant	Intron 1 of 12			ENSP00000499045.1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84925 AN: 151812 Hom.: 24396 Cov.: 32

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.559 AC: 84966 AN: 151928 Hom.: 24407 Cov.: 32 AF XY: 0.554 AC XY: 41135 AN XY: 74224

African (AFR) AF: 0.581 AC: 24075 AN: 41428

American (AMR) AF: 0.509 AC: 7768 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2031 AN: 3468

East Asian (EAS) AF: 0.163 AC: 841 AN: 5166

South Asian (SAS) AF: 0.494 AC: 2382 AN: 4822

European-Finnish (FIN) AF: 0.570 AC: 5991 AN: 10512

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.586 AC: 39799 AN: 67968

Other (OTH) AF: 0.571 AC: 1204 AN: 2110

Alfa AF: 0.575 Hom.: 39280

Bravo AF: 0.551

Asia WGS AF: 0.370 AC: 1285 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	1.5
DANN	Benign	0.74
PhyloP100		-0.43
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: rs7826312; hg19: chr8-32400115;