dbSNP rs7834206: NRG1:c.-97C>A (chr8-32548630-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013964.5(NRG1):c.-97C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,443,660 control chromosomes in the GnomAD database, including 142,735 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 0.39 ( 12745 hom., cov: 34)

Exomes 𝑓: 0.44 ( 129990 hom. )

Consequence

NRG1
NM_013964.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.349

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_013964.5 link	c.-97C>A		5_prime_UTR_variant	Exon 1 of 12	ENST00000405005.8	NP_039258.1	Q02297-1Q6PK61

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000405005 link	c.-97C>A		5_prime_UTR_variant	Exon 1 of 12	1	NM_013964.5	ENSP00000384620.2		Q02297-1

Frequencies

GnomAD3 genomes

AF:

0.392

AC:

59514

AN:

151914

Hom.:

12738

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.450

Gnomad AMR

AF:

0.485

Gnomad ASJ

AF:

0.387

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.557

Gnomad MID

AF:

0.352

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.386

GnomAD4 exome

AF:

0.443

AC:

572649

AN:

1291634

Hom.:

129990

Cov.:

AF XY:

0.443

AC XY:

279287

AN XY:

630242

show subpopulations

Gnomad4 AFR exome

AF:

0.217

Gnomad4 AMR exome

AF:

0.526

Gnomad4 ASJ exome

AF:

0.375

Gnomad4 EAS exome

AF:

0.195

Gnomad4 SAS exome

AF:

0.416

Gnomad4 FIN exome

AF:

0.554

Gnomad4 NFE exome

AF:

0.456

Gnomad4 OTH exome

AF:

0.411

GnomAD4 genome

AF:

0.392

AC:

59544

AN:

152026

Hom.:

12745

Cov.:

AF XY:

0.395

AC XY:

29338

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.230

Gnomad4 AMR

AF:

0.485

Gnomad4 ASJ

AF:

0.387

Gnomad4 EAS

AF:

0.175

Gnomad4 SAS

AF:

0.408

Gnomad4 FIN

AF:

0.557

Gnomad4 NFE

AF:

0.459

Gnomad4 OTH

AF:

0.387

Alfa

AF:

0.289

Hom.:

946

Bravo

AF:

0.379

Asia WGS

AF:

0.342

AC:

1189

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.6

DANN

Benign

0.69

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over