rs6988339

Variant names:

• chr8-32688398-G-A
• rs6988339
• NM_013964.5:c.503-39551G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-32688398-G-A
• chr8-32688398-G-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.503-39551G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 151,980 control chromosomes in the GnomAD database, including 36,032 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 0.68 (36032 hom., cov: 31)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.360
• Publications: 13 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_013964.5	c.503-39551G>A		intron_variant	Intron 5 of 11	ENST00000405005.8	NP_039258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000405005.8	c.503-39551G>A		intron_variant	Intron 5 of 11	1	NM_013964.5	ENSP00000384620.2

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102491 AN: 151864 Hom.: 35976 Cov.: 31

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.675 AC: 102598 AN: 151980 Hom.: 36032 Cov.: 31 AF XY: 0.671 AC XY: 49829 AN XY: 74268

African (AFR) AF: 0.887 AC: 36800 AN: 41484

American (AMR) AF: 0.601 AC: 9165 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2284 AN: 3468

East Asian (EAS) AF: 0.485 AC: 2497 AN: 5144

South Asian (SAS) AF: 0.541 AC: 2599 AN: 4806

European-Finnish (FIN) AF: 0.618 AC: 6522 AN: 10546

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.597 AC: 40563 AN: 67960

Other (OTH) AF: 0.651 AC: 1370 AN: 2106

Alfa AF: 0.615 Hom.: 22163

Bravo AF: 0.686

Asia WGS AF: 0.551 AC: 1916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.4
DANN	Benign	0.64
PhyloP100		0.36
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: rs6988339; hg19: chr8-32545916;