ENST00000520407.5:c.745+398347T>C

Variant names:

• chr8-32039076-T-C
• rs1462906
• ENST00000520407.5:c.745+398347T>C

Variant summary

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

The ENST00000520407.5(NRG1):​c.745+398347T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 152,156 control chromosomes in the GnomAD database, including 53,871 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 0.79 (53871 hom., cov: 32)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.764
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_001159999.3	c.37+399645T>C		intron_variant	Intron 1 of 12		NP_001153471.1
NRG1	NM_001159995.3	c.37+399645T>C		intron_variant	Intron 1 of 11		NP_001153467.1
NRG1	NM_001160001.3	c.37+399645T>C		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.745+398347T>C		intron_variant	Intron 1 of 4	1		ENSP00000434640.1
NRG1-IT1	ENST00000521463.6	n.253+9591T>C		intron_variant	Intron 2 of 3	1
NRG1	ENST00000523534.5	c.304+398347T>C		intron_variant	Intron 1 of 12	5		ENSP00000429067.1

Frequencies

GnomAD3 genomes AF: 0.793 AC: 120635 AN: 152038 Hom.: 53857 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.908

Gnomad ASJ AF: 0.935

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.955

Gnomad FIN AF: 0.979

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.976

Gnomad OTH AF: 0.825

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

GnomAD4 genome AF: 0.793 AC: 120678 AN: 152156 Hom.: 53871 Cov.: 32 AF XY: 0.800 AC XY: 59517 AN XY: 74380

African (AFR) AF: 0.340 AC: 14107 AN: 41436

American (AMR) AF: 0.908 AC: 13890 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.935 AC: 3246 AN: 3472

East Asian (EAS) AF: 0.995 AC: 5146 AN: 5172

South Asian (SAS) AF: 0.956 AC: 4605 AN: 4816

European-Finnish (FIN) AF: 0.979 AC: 10398 AN: 10618

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.976 AC: 66384 AN: 68024

Other (OTH) AF: 0.827 AC: 1750 AN: 2116

Alfa AF: 0.770 Hom.: 25082

Bravo AF: 0.767

Asia WGS AF: 0.932 AC: 3242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.8
DANN	Benign	0.60
PhyloP100		-0.76
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: rs1462906; hg19: chr8-31896592;