Genetic Variant NRG1:c.804-26delA (chr8-32756368-CA-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_013964.5(NRG1):c.804-26delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,570,332 control chromosomes in the GnomAD database, including 1,660 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.058 ( 861 hom., cov: 31)

Exomes 𝑓: 0.0060 ( 799 hom. )

Consequence

NRG1
NM_013964.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.05

Publications

1 publications found

Variant links:

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

NRG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_013964.5 link	c.804-26delA		intron_variant	Intron 8 of 11	ENST00000405005.8	NP_039258.1	Q02297-1Q6PK61

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000405005.8 link	c.804-26delA		intron_variant	Intron 8 of 11	1	NM_013964.5	ENSP00000384620.2		Q02297-1

Frequencies

GnomAD3 genomes

AF:

0.0579

AC:

8712

AN:

150358

Hom.:

860

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0178

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00232

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000607

Gnomad OTH

AF:

0.0364

GnomAD2 exomes

AF:

0.0191

AC:

3826

AN:

199974

AF XY:

0.0145

show subpopulations

Gnomad AFR exome

AF:

0.221

Gnomad AMR exome

AF:

0.0115

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.000547

Gnomad FIN exome

AF:

0.000531

Gnomad NFE exome

AF:

0.00121

Gnomad OTH exome

AF:

0.00909

GnomAD4 exome

AF:

0.00603

AC:

8562

AN:

1419864

Hom.:

799

Cov.:

AF XY:

0.00529

AC XY:

3735

AN XY:

705904

show subpopulations

African (AFR)

AF:

0.214

AC:

6775

AN:

31732

American (AMR)

AF:

0.0112

AC:

452

AN:

40334

Ashkenazi Jewish (ASJ)

AF:

0.000366

AC:

AN:

24606

East Asian (EAS)

AF:

0.000285

AC:

AN:

38536

South Asian (SAS)

AF:

0.00237

AC:

194

AN:

81810

European-Finnish (FIN)

AF:

0.000156

AC:

AN:

51342

Middle Eastern (MID)

AF:

0.00614

AC:

AN:

5534

European-Non Finnish (NFE)

AF:

0.000352

AC:

383

AN:

1087616

Other (OTH)

AF:

0.0119

AC:

696

AN:

58354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

329

658

988

1317

1646

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

218

436

654

872

1090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0581

AC:

8736

AN:

150468

Hom.:

861

Cov.:

AF XY:

0.0559

AC XY:

4105

AN XY:

73388

show subpopulations

African (AFR)

AF:

0.203

AC:

8338

AN:

41076

American (AMR)

AF:

0.0178

AC:

269

AN:

15120

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

5122

South Asian (SAS)

AF:

0.00232

AC:

AN:

4742

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10180

Middle Eastern (MID)

AF:

0.00690

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000607

AC:

AN:

67504

Other (OTH)

AF:

0.0361

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

349

697

1046

1394

1743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00656

Hom.:

Bravo

AF:

0.0655

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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8-32756368-CAA-CA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over