rs10503906

Variant names:

• chr8-32314446-G-A
• rs10503906
• ENST00000520407.5:c.746-281382G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001159999.3(NRG1):​c.38-281382G>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 NM_001159999.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.697
• Publications: 3 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: Likely_benign. The variant received -4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159999.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	NM_001159999.3		c.38-281382G>A		intron	N/A	NP_001153471.1	A0A494C1F5
	NRG1	NM_001159995.3		c.38-281382G>A		intron	N/A	NP_001153467.1	A0A494C1F8
	NRG1	NM_001160001.3		c.38-281382G>A		intron	N/A	NP_001153473.1	Q02297-11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	ENST00000520407.5	TSL:1	c.746-281382G>A		intron	N/A	ENSP00000434640.1	Q02297-9
	NRG1	ENST00000523534.5	TSL:5	c.305-281382G>A		intron	N/A	ENSP00000429067.1	H0YBA3
	NRG1	ENST00000650866.1		c.38-281382G>A		intron	N/A	ENSP00000499045.1	A0A494C1F5

Frequencies

GnomAD3 genomes AF: 0.439 AC: 19673 AN: 44764 Hom.: 1552 Cov.: 0

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

African (AFR) AF: 0.431 AC: 1786 AN: 4148

American (AMR) AF: 0.483 AC: 2423 AN: 5016

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 563 AN: 1104

East Asian (EAS) AF: 0.512 AC: 478 AN: 934

South Asian (SAS) AF: 0.548 AC: 1001 AN: 1826

European-Finnish (FIN) AF: 0.415 AC: 2054 AN: 4948

Middle Eastern (MID) AF: 0.512 AC: 41 AN: 80

European-Non Finnish (NFE) AF: 0.421 AC: 10714 AN: 25472

Other (OTH) AF: 0.427 AC: 233 AN: 546

Alfa AF: 0.141 Hom.: 258

Bravo AF: 0.122

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.2
DANN	Benign	0.81
PhyloP100		0.70
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: rs10503906; hg19: chr8-32171962;