rs1386438

Variant names:

• chr8-32338027-T-G
• rs1386438
• ENST00000520407.5:c.746-257801T>G

Variant summary

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

The ENST00000520407.5(NRG1):​c.746-257801T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 151,984 control chromosomes in the GnomAD database, including 21,900 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 0.53 (21900 hom., cov: 32)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_001159999.3	c.38-257801T>G		intron_variant	Intron 1 of 12		NP_001153471.1
NRG1	NM_001159995.3	c.38-257801T>G		intron_variant	Intron 1 of 11		NP_001153467.1
NRG1	NM_001160001.3	c.38-257801T>G		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.746-257801T>G		intron_variant	Intron 1 of 4	1		ENSP00000434640.1
NRG1	ENST00000523534.5	c.305-257801T>G		intron_variant	Intron 1 of 12	5		ENSP00000429067.1
NRG1	ENST00000650866.1	c.38-257801T>G		intron_variant	Intron 1 of 12			ENSP00000499045.1

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80180 AN: 151864 Hom.: 21895 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.528 AC: 80212 AN: 151984 Hom.: 21900 Cov.: 32 AF XY: 0.522 AC XY: 38762 AN XY: 74306

African (AFR) AF: 0.426 AC: 17668 AN: 41442

American (AMR) AF: 0.459 AC: 7007 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1679 AN: 3464

East Asian (EAS) AF: 0.324 AC: 1674 AN: 5160

South Asian (SAS) AF: 0.590 AC: 2846 AN: 4824

European-Finnish (FIN) AF: 0.538 AC: 5679 AN: 10556

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.614 AC: 41737 AN: 67948

Other (OTH) AF: 0.520 AC: 1098 AN: 2112

Alfa AF: 0.565 Hom.: 6272

Bravo AF: 0.511

Asia WGS AF: 0.495 AC: 1722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.6
DANN	Benign	0.66
PhyloP100		0.096
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: rs1386438; hg19: chr8-32195543;