8-32125908-G-T

Variant names:

• chr8-32125908-G-T
• rs2346771
• ENST00000520407.5:c.746-469920G>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.38-469920G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 151,800 control chromosomes in the GnomAD database, including 34,178 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 0.66 (34178 hom., cov: 32)
• Consequence: NRG1 NM_001159999.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303
• 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-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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 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.38-469920G>T		intron	N/A	NP_001153471.1	A0A494C1F5
	NRG1	NM_001159995.3		c.38-469920G>T		intron	N/A	NP_001153467.1	A0A494C1F8
	NRG1	NM_001160001.3		c.38-469920G>T		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.746-469920G>T		intron	N/A	ENSP00000434640.1	Q02297-9
	NRG1	ENST00000523534.5	TSL:5	c.305-469920G>T		intron	N/A	ENSP00000429067.1	H0YBA3
	NRG1	ENST00000650866.1		c.38-469920G>T		intron	N/A	ENSP00000499045.1	A0A494C1F5

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99791 AN: 151682 Hom.: 34127 Cov.: 32

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.658 AC: 99907 AN: 151800 Hom.: 34178 Cov.: 32 AF XY: 0.658 AC XY: 48848 AN XY: 74198

African (AFR) AF: 0.852 AC: 35334 AN: 41472

American (AMR) AF: 0.691 AC: 10523 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1886 AN: 3462

East Asian (EAS) AF: 0.490 AC: 2515 AN: 5132

South Asian (SAS) AF: 0.649 AC: 3133 AN: 4824

European-Finnish (FIN) AF: 0.603 AC: 6357 AN: 10536

Middle Eastern (MID) AF: 0.610 AC: 178 AN: 292

European-Non Finnish (NFE) AF: 0.564 AC: 38274 AN: 67842

Other (OTH) AF: 0.624 AC: 1314 AN: 2106

Alfa AF: 0.591 Hom.: 12129

Bravo AF: 0.671

Asia WGS AF: 0.592 AC: 2061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.20
PhyloP100		0.30
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: rs2346771; hg19: chr8-31983424;