8-32168933-C-T

Variant names:

• chr8-32168933-C-T
• rs10093107
• ENST00000520407.5:c.746-426895C>T

Variant summary

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

The NM_001159999.3(NRG1):​c.38-426895C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 151,978 control chromosomes in the GnomAD database, including 16,971 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 0.45 (16971 hom., cov: 32)
• Consequence: NRG1 NM_001159999.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

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.38-426895C>T		intron	N/A	NP_001153471.1
	NRG1	NM_001159995.3		c.38-426895C>T		intron	N/A	NP_001153467.1
	NRG1	NM_001160001.3		c.38-426895C>T		intron	N/A	NP_001153473.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	ENST00000520407.5	TSL:1	c.746-426895C>T		intron	N/A	ENSP00000434640.1
	NRG1	ENST00000523534.5	TSL:5	c.305-426895C>T		intron	N/A	ENSP00000429067.1
	NRG1	ENST00000650866.1		c.38-426895C>T		intron	N/A	ENSP00000499045.1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67855 AN: 151860 Hom.: 16961 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.447 AC: 67890 AN: 151978 Hom.: 16971 Cov.: 32 AF XY: 0.449 AC XY: 33344 AN XY: 74274

African (AFR) AF: 0.231 AC: 9564 AN: 41458

American (AMR) AF: 0.566 AC: 8638 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1668 AN: 3470

East Asian (EAS) AF: 0.209 AC: 1078 AN: 5164

South Asian (SAS) AF: 0.437 AC: 2103 AN: 4812

European-Finnish (FIN) AF: 0.565 AC: 5960 AN: 10548

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.549 AC: 37287 AN: 67968

Other (OTH) AF: 0.443 AC: 933 AN: 2104

Alfa AF: 0.509 Hom.: 12347

Bravo AF: 0.438

Asia WGS AF: 0.320 AC: 1117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.53
PhyloP100		0.049
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: rs10093107; hg19: chr8-32026449;