rs10503906

Positions:

• chr8-32314446-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000520407.5(NRG1):​c.746-281382G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.44 (1552 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.697

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRG1	NM_001159995.3	c.38-281382G>A		intron_variant			NP_001153467.1
NRG1	NM_001159999.3	c.38-281382G>A		intron_variant			NP_001153471.1
NRG1	NM_001160001.3	c.38-281382G>A		intron_variant			NP_001153473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000520407.5	c.746-281382G>A		intron_variant		1		ENSP00000434640
NRG1	ENST00000519301.6	c.38-281382G>A		intron_variant		5		ENSP00000429582
NRG1	ENST00000523534.5	c.305-281382G>A		intron_variant		5		ENSP00000429067

Frequencies

GnomAD3 genomes AF: 0.00 AC: 19673 AN: 44764 Hom.: 1552 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.512

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.424

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.439 AC: 19677 AN: 44774 Hom.: 1552 Cov.: 0 AF XY: 0.445 AC XY: 9961 AN XY: 22362

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.427

Alfa AF: 0.141 Hom.: 258

Bravo AF: 0.122

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.2
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10503906; hg19: chr8-32171962;