8-32553981-G-C

Variant names:

• chr8-32553981-G-C
• rs7835688
• NM_013964.5:c.100+5155G>C

Variant summary

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

The NM_013964.5(NRG1):​c.100+5155G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 151,894 control chromosomes in the GnomAD database, including 12,739 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 (12739 hom., cov: 32)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 30 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=-0.92).
• 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	c.100+5155G>C		intron_variant	Intron 1 of 11	ENST00000405005.8	NP_039258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000405005.8	c.100+5155G>C		intron_variant	Intron 1 of 11	1	NM_013964.5	ENSP00000384620.2

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59517 AN: 151778 Hom.: 12732 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.392 AC: 59548 AN: 151894 Hom.: 12739 Cov.: 32 AF XY: 0.395 AC XY: 29330 AN XY: 74210

African (AFR) AF: 0.231 AC: 9558 AN: 41412

American (AMR) AF: 0.485 AC: 7406 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1342 AN: 3470

East Asian (EAS) AF: 0.176 AC: 908 AN: 5166

South Asian (SAS) AF: 0.408 AC: 1965 AN: 4812

European-Finnish (FIN) AF: 0.558 AC: 5870 AN: 10520

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31163 AN: 67944

Other (OTH) AF: 0.388 AC: 817 AN: 2106

Alfa AF: 0.294 Hom.: 828

Bravo AF: 0.379

Asia WGS AF: 0.341 AC: 1185 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.094
DANN	Benign	0.48
PhyloP100		-1.9
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: rs7835688; hg19: chr8-32411499;