rs6988339

chr8-32688398-G-Achr8-32688398-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
NRG1	NM_013964.5	c.503-39551G>A		intron_variant		ENST00000405005.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1	ENST00000405005.8	c.503-39551G>A		intron_variant		1	NM_013964.5	A2

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

Gnomad4 AFR AF: 0.887

Gnomad4 AMR AF: 0.601

Gnomad4 ASJ AF: 0.659

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.651

Alfa AF: 0.612 Hom.: 15529

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6988339; hg19: chr8-32545916;