Genetic Variant ENST00000520407.5:c.360G>T (chr8-31640344-G-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The ENST00000520407.5(NRG1):c.360G>T(p.Ala120Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000025 in 1,198,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

NRG1
ENST00000520407.5 synonymous

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -1.06

Publications

0 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:

ENSG00000302325 (HGNC:):

ENSG00000302325 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP7

Synonymous conserved (PhyloP=-1.06 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
NRG1	NM_013962.3 link	c.360G>T	p.Ala120Ala	synonymous_variant	Exon 1 of 5	NP_039256.2	Q02297-9
NRG1	XM_011544512.3 link	c.360G>T	p.Ala120Ala	synonymous_variant	Exon 1 of 13	XP_011542814.2
NRG1	XM_017013367.2 link	c.360G>T	p.Ala120Ala	synonymous_variant	Exon 1 of 11	XP_016868856.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
NRG1	ENST00000520407.5 link	c.360G>T	p.Ala120Ala	synonymous_variant	Exon 1 of 5	1	ENSP00000434640.1	Q02297-9
NRG1	ENST00000650866.1 link	c.37+913G>T		intron_variant	Intron 1 of 12		ENSP00000499045.1	A0A494C1F5
NRG1	ENST00000652698.1 link	c.37+913G>T		intron_variant	Intron 1 of 11		ENSP00000499008.1	A0A494C1F8

Frequencies

GnomAD3 genomes

AF:

0.0000803

AC:

AN:

149376

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000219

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000448

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000172

AC:

AN:

1048792

Hom.:

Cov.:

AF XY:

0.0000202

AC XY:

AN XY:

496188

show subpopulations

African (AFR)

AF:

0.000513

AC:

AN:

21450

American (AMR)

AF:

0.00

AC:

AN:

7166

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12468

East Asian (EAS)

AF:

0.00

AC:

AN:

23270

South Asian (SAS)

AF:

0.00

AC:

AN:

19412

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20896

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2704

European-Non Finnish (NFE)

AF:

0.00000666

AC:

AN:

900522

Other (OTH)

AF:

0.0000244

AC:

AN:

40904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000803

AC:

AN:

149376

Hom.:

Cov.:

AF XY:

0.0000687

AC XY:

AN XY:

72798

show subpopulations

African (AFR)

AF:

0.000219

AC:

AN:

41146

American (AMR)

AF:

0.00

AC:

AN:

15002

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3432

East Asian (EAS)

AF:

0.00

AC:

AN:

5110

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000448

AC:

AN:

67000

Other (OTH)

AF:

0.00

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.546

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000907

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

Psychiatry Genetics Yale University

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

-1.1

PromoterAI

-0.043

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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ENST00000520407.5:c.360G>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over