rs2439272

chr8-32635573-A-Gchr8-32635573-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP5 BP4 BA1

The NM_013964.5(NRG1):c.502+18688A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 151,912 control chromosomes in the GnomAD database, including 38,494 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely pathogenic (no stars).

• Frequency: Genomes: 𝑓 0.70 (38494 hom., cov: 31)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.565

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 -8 ACMG points.

• PP5: Variant 8-32635573-A-G is Pathogenic according to our data. Variant chr8-32635573-A-G is described in Lovd as [Likely_pathogenic].
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).. Strength limited to SUPPORTING due to the PP5.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG1	NM_013964.5	c.502+18688A>G		intron_variant		ENST00000405005.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1	ENST00000405005.8	c.502+18688A>G		intron_variant		1	NM_013964.5	A2

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106660 AN: 151794 Hom.: 38439 Cov.: 31

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.703 AC: 106769 AN: 151912 Hom.: 38494 Cov.: 31 AF XY: 0.705 AC XY: 52303 AN XY: 74220

Gnomad4 AFR AF: 0.858

Gnomad4 AMR AF: 0.752

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.790

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.676

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.684

Alfa AF: 0.634 Hom.: 7031

Bravo AF: 0.720

Asia WGS AF: 0.676 AC: 2351 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	0.90
Dann	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2439272; hg19: chr8-32493092;