8-32571241-C-T

Variant names:

• chr8-32571241-C-T
• rs4236710
• NM_013964.5:c.100+22415C>T

Variant summary

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

The NM_013964.5(NRG1):​c.100+22415C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 152,052 control chromosomes in the GnomAD database, including 26,429 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 0.58 (26429 hom., cov: 33)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.496
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013964.5. 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_013964.5	MANE Select	c.100+22415C>T		intron	N/A	NP_039258.1	Q02297-1
	NRG1	NM_013956.5		c.100+22415C>T		intron	N/A	NP_039250.2	Q02297-6
	NRG1	NM_013957.5		c.100+22415C>T		intron	N/A	NP_039251.2	Q02297-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	ENST00000405005.8	TSL:1 MANE Select	c.100+22415C>T		intron	N/A	ENSP00000384620.2	Q02297-1
	NRG1	ENST00000287842.7	TSL:1	c.100+22415C>T		intron	N/A	ENSP00000287842.4	Q02297-6
	NRG1	ENST00000356819.7	TSL:1	c.100+22415C>T		intron	N/A	ENSP00000349275.6	Q02297-7

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88540 AN: 151934 Hom.: 26406 Cov.: 33

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.583 AC: 88608 AN: 152052 Hom.: 26429 Cov.: 33 AF XY: 0.587 AC XY: 43588 AN XY: 74318

African (AFR) AF: 0.494 AC: 20472 AN: 41446

American (AMR) AF: 0.635 AC: 9711 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2028 AN: 3470

East Asian (EAS) AF: 0.849 AC: 4402 AN: 5182

South Asian (SAS) AF: 0.708 AC: 3412 AN: 4816

European-Finnish (FIN) AF: 0.577 AC: 6088 AN: 10558

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.599 AC: 40737 AN: 67988

Other (OTH) AF: 0.594 AC: 1250 AN: 2104

Alfa AF: 0.585 Hom.: 5321

Bravo AF: 0.585

Asia WGS AF: 0.726 AC: 2526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.3
DANN	Benign	0.49
PhyloP100		0.50
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: rs4236710; hg19: chr8-32428759;