dbSNP rs3735781: NRG1:c.*2908A>G (chr8-32767310-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013964.5(NRG1):c.*2908A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 151,992 control chromosomes in the GnomAD database, including 11,514 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 0.38 ( 11514 hom., cov: 32)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

NRG1
NM_013964.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.105

Publications

11 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

new If you want to explore the variant's impact on the transcript NM_013964.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013964.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NRG1	NM_013964.5	MANE Select	c.*2908A>G	3_prime_UTR	Exon 12 of 12	NP_039258.1	Q02297-1
NRG1	NM_001322205.2		c.*2908A>G	3_prime_UTR	Exon 9 of 9	NP_001309134.1	A0A494C0Q4
NRG1	NM_013956.5		c.*2908A>G	3_prime_UTR	Exon 13 of 13	NP_039250.2	Q02297-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NRG1	ENST00000405005.8	TSL:1 MANE Select	c.*2908A>G	3_prime_UTR	Exon 12 of 12	ENSP00000384620.2	Q02297-1
NRG1	ENST00000356819.7	TSL:1	c.*2908A>G	3_prime_UTR	Exon 12 of 12	ENSP00000349275.6	Q02297-7
NRG1	ENST00000652592.1		c.*2908A>G	3_prime_UTR	Exon 9 of 9	ENSP00000498646.1	A0A494C0Q4

Frequencies

GnomAD3 genomes

AF:

0.385

AC:

58435

AN:

151870

Hom.:

11496

Cov.:

show subpopulations

Gnomad AFR

AF:

0.386

Gnomad AMI

AF:

0.499

Gnomad AMR

AF:

0.307

Gnomad ASJ

AF:

0.373

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.338

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.424

Gnomad OTH

AF:

0.396

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.385

AC:

58490

AN:

151988

Hom.:

11514

Cov.:

AF XY:

0.376

AC XY:

27897

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.386

AC:

15993

AN:

41426

American (AMR)

AF:

0.307

AC:

4679

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

1293

AN:

3468

East Asian (EAS)

AF:

0.199

AC:

1027

AN:

5166

South Asian (SAS)

AF:

0.342

AC:

1646

AN:

4816

European-Finnish (FIN)

AF:

0.338

AC:

3559

AN:

10542

Middle Eastern (MID)

AF:

0.452

AC:

133

AN:

294

European-Non Finnish (NFE)

AF:

0.424

AC:

28857

AN:

68000

Other (OTH)

AF:

0.402

AC:

848

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1825

3649

5474

7298

9123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

548

1096

1644

2192

2740

<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:

0.403

Hom.:

15775

Bravo

AF:

0.379

Asia WGS

AF:

0.298

AC:

1041

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.1

(source)

DANN

Benign

0.68

PhyloP100

0.10

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over