8-32133711-T-C

Variant names:

• chr8-32133711-T-C
• rs1481762
• ENST00000520407.5:c.746-462117T>C

Variant summary

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

The NM_001159999.3(NRG1):​c.38-462117T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 151,982 control chromosomes in the GnomAD database, including 28,921 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 0.61 (28921 hom., cov: 32)
• Consequence: NRG1 NM_001159999.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.96
• Publications: 5 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-IT1 (HGNC:43633): (NRG1 intronic transcript 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.696 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.38-462117T>C		intron	N/A	NP_001153471.1	A0A494C1F5
	NRG1	NM_001159995.3		c.38-462117T>C		intron	N/A	NP_001153467.1	A0A494C1F8
	NRG1	NM_001160001.3		c.38-462117T>C		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.746-462117T>C		intron	N/A	ENSP00000434640.1	Q02297-9
	NRG1	ENST00000523534.5	TSL:5	c.305-462117T>C		intron	N/A	ENSP00000429067.1	H0YBA3
	NRG1	ENST00000650866.1		c.38-462117T>C		intron	N/A	ENSP00000499045.1	A0A494C1F5

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92837 AN: 151864 Hom.: 28890 Cov.: 32

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.611 AC: 92915 AN: 151982 Hom.: 28921 Cov.: 32 AF XY: 0.611 AC XY: 45384 AN XY: 74276

African (AFR) AF: 0.703 AC: 29136 AN: 41442

American (AMR) AF: 0.677 AC: 10321 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1931 AN: 3472

East Asian (EAS) AF: 0.437 AC: 2254 AN: 5154

South Asian (SAS) AF: 0.549 AC: 2644 AN: 4816

European-Finnish (FIN) AF: 0.603 AC: 6375 AN: 10578

Middle Eastern (MID) AF: 0.603 AC: 176 AN: 292

European-Non Finnish (NFE) AF: 0.566 AC: 38483 AN: 67952

Other (OTH) AF: 0.591 AC: 1249 AN: 2114

Alfa AF: 0.583 Hom.: 44371

Bravo AF: 0.621

Asia WGS AF: 0.505 AC: 1757 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	15
DANN	Benign	0.81
PhyloP100		3.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1481762;

hg19: chr8-31991227;