rs2954041

chr8-32665107-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013964.5(NRG1):c.502+48222G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0521 in 152,188 control chromosomes in the GnomAD database, including 642 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 0.052 (642 hom., cov: 32)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.566

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG1	NM_013964.5	c.502+48222G>T		intron_variant		ENST00000405005.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1	ENST00000405005.8	c.502+48222G>T		intron_variant		1	NM_013964.5	A2

Frequencies

GnomAD3 genomes AF: 0.0522 AC: 7931 AN: 152070 Hom.: 644 Cov.: 32

Gnomad AFR AF: 0.0518

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.0868

Gnomad FIN AF: 0.0208

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0142

Gnomad OTH AF: 0.0492

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

GnomAD4 genome AF: 0.0521 AC: 7934 AN: 152188 Hom.: 642 Cov.: 32 AF XY: 0.0555 AC XY: 4131 AN XY: 74406

Gnomad4 AFR AF: 0.0518

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.0864

Gnomad4 FIN AF: 0.0208

Gnomad4 NFE AF: 0.0142

Gnomad4 OTH AF: 0.0482

Alfa AF: 0.0520 Hom.: 104

Bravo AF: 0.0639

Asia WGS AF: 0.187 AC: 651 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.4
Dann	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2954041; hg19: chr8-32522626;