rs10113578

Variant names:

• chr8-32526611-G-A
• rs10113578
• ENST00000520407.5:c.746-69217G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-32526611-G-A
• chr8-32526611-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000520407.5(NRG1):​c.746-69217G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,020 control chromosomes in the GnomAD database, including 2,466 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 0.11 (2466 hom., cov: 32)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000520407.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	NM_001159999.3		c.38-69217G>A		intron	N/A	NP_001153471.1
	NRG1	NM_001159995.3		c.38-69217G>A		intron	N/A	NP_001153467.1
	NRG1	NM_001160001.3		c.38-69217G>A		intron	N/A	NP_001153473.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	ENST00000520407.5	TSL:1	c.746-69217G>A		intron	N/A	ENSP00000434640.1
	NRG1	ENST00000523534.5	TSL:5	c.305-69217G>A		intron	N/A	ENSP00000429067.1
	NRG1	ENST00000650866.1		c.38-69217G>A		intron	N/A	ENSP00000499045.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17374 AN: 151902 Hom.: 2450 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0925

Gnomad ASJ AF: 0.0438

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.0982

Gnomad FIN AF: 0.0172

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0191

Gnomad OTH AF: 0.0984

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

GnomAD4 genome AF: 0.115 AC: 17428 AN: 152020 Hom.: 2466 Cov.: 32 AF XY: 0.116 AC XY: 8650 AN XY: 74326

African (AFR) AF: 0.260 AC: 10751 AN: 41396

American (AMR) AF: 0.0928 AC: 1418 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0438 AC: 152 AN: 3472

East Asian (EAS) AF: 0.575 AC: 2947 AN: 5124

South Asian (SAS) AF: 0.0976 AC: 469 AN: 4804

European-Finnish (FIN) AF: 0.0172 AC: 183 AN: 10614

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0191 AC: 1298 AN: 68010

Other (OTH) AF: 0.0959 AC: 203 AN: 2116

Alfa AF: 0.0760 Hom.: 155

Bravo AF: 0.131

Asia WGS AF: 0.258 AC: 896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.55
PhyloP100		-0.20
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: rs10113578; hg19: chr8-32384128;