rs1481737

Variant names:

• chr8-32119713-A-G
• rs1481737
• ENST00000520407.5:c.746-476115A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-32119713-A-G
• chr8-32119713-A-T

Variant summary

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

The ENST00000520407.5(NRG1):​c.746-476115A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 151,816 control chromosomes in the GnomAD database, including 42,832 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 0.75 (42832 hom., cov: 31)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_001159999.3	c.38-476115A>G		intron_variant	Intron 1 of 12		NP_001153471.1
NRG1	NM_001159995.3	c.38-476115A>G		intron_variant	Intron 1 of 11		NP_001153467.1
NRG1	NM_001160001.3	c.38-476115A>G		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.746-476115A>G		intron_variant	Intron 1 of 4	1		ENSP00000434640.1
NRG1-IT1	ENST00000840252.1	n.330A>G		non_coding_transcript_exon_variant	Exon 3 of 3
NRG1	ENST00000523534.5	c.305-476115A>G		intron_variant	Intron 1 of 12	5		ENSP00000429067.1

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113280 AN: 151698 Hom.: 42804 Cov.: 31

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.783

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.747 AC: 113356 AN: 151816 Hom.: 42832 Cov.: 31 AF XY: 0.744 AC XY: 55164 AN XY: 74172

African (AFR) AF: 0.823 AC: 34058 AN: 41406

American (AMR) AF: 0.822 AC: 12520 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2293 AN: 3464

East Asian (EAS) AF: 0.494 AC: 2532 AN: 5122

South Asian (SAS) AF: 0.655 AC: 3151 AN: 4812

European-Finnish (FIN) AF: 0.718 AC: 7586 AN: 10570

Middle Eastern (MID) AF: 0.764 AC: 223 AN: 292

European-Non Finnish (NFE) AF: 0.721 AC: 48925 AN: 67900

Other (OTH) AF: 0.757 AC: 1599 AN: 2112

Alfa AF: 0.726 Hom.: 21660

Bravo AF: 0.759

Asia WGS AF: 0.602 AC: 2093 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.82
PhyloP100		-0.35
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: rs1481737; hg19: chr8-31977229;