rs10094655

Variant names:

• chr8-32536630-T-A
• rs10094655
• ENST00000520407.5:c.746-59198T>A

Your query was ambiguous. Multiple possible variants found:

• chr8-32536630-T-A
• chr8-32536630-T-G

Variant summary

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

The ENST00000520407.5(NRG1):​c.746-59198T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 151,870 control chromosomes in the GnomAD database, including 2,335 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 (2335 hom., cov: 32)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.612
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_001159999.3	c.38-59198T>A		intron_variant	Intron 1 of 12		NP_001153471.1
NRG1	NM_001159995.3	c.38-59198T>A		intron_variant	Intron 1 of 11		NP_001153467.1
NRG1	NM_001160001.3	c.38-59198T>A		intron_variant	Intron 1 of 10		NP_001153473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000520407.5	c.746-59198T>A		intron_variant	Intron 1 of 4	1		ENSP00000434640.1
NRG1	ENST00000523534.5	c.305-59198T>A		intron_variant	Intron 1 of 12	5		ENSP00000429067.1
NRG1	ENST00000650866.1	c.38-59198T>A		intron_variant	Intron 1 of 12			ENSP00000499045.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16701 AN: 151752 Hom.: 2323 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0887

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.0986

Gnomad FIN AF: 0.0173

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0187

Gnomad OTH AF: 0.0932

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

GnomAD4 genome AF: 0.110 AC: 16739 AN: 151870 Hom.: 2335 Cov.: 32 AF XY: 0.112 AC XY: 8320 AN XY: 74246

African (AFR) AF: 0.245 AC: 10159 AN: 41398

American (AMR) AF: 0.0890 AC: 1359 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 85 AN: 3466

East Asian (EAS) AF: 0.589 AC: 3011 AN: 5110

South Asian (SAS) AF: 0.0980 AC: 472 AN: 4814

European-Finnish (FIN) AF: 0.0173 AC: 183 AN: 10568

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

European-Non Finnish (NFE) AF: 0.0187 AC: 1272 AN: 67936

Other (OTH) AF: 0.0908 AC: 191 AN: 2104

Alfa AF: 0.0645 Hom.: 115

Bravo AF: 0.126

Asia WGS AF: 0.256 AC: 891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.1
DANN	Benign	0.93
PhyloP100		0.61
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: rs10094655; hg19: chr8-32394147;