rs770519581

Variant names:

• chr8-31640283-AGGCGGCGGC-A
• rs770519581
• ENST00000520407.5:c.308_316delCGGCGGCGG

Your query was ambiguous. Multiple possible variants found:

• chr8-31640283-AGGCGGCGGC-A
• chr8-31640283-AGGCGGCGGC-AGGCGGC
• chr8-31640283-AGGCGGCGGC-AGGCGGCGGCGGC
• chr8-31640283-AGGCGGCGGC-AGGCGGCGGCGGCGGC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_013962.3(NRG1):​c.308_316delCGGCGGCGG​(p.Ala103_Ala105del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000678 in 147,444 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NRG1 NM_013962.3 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.54

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_013962.3	c.308_316delCGGCGGCGG	p.Ala103_Ala105del	disruptive_inframe_deletion	Exon 1 of 5		NP_039256.2
NRG1	XM_011544512.3	c.308_316delCGGCGGCGG	p.Ala103_Ala105del	disruptive_inframe_deletion	Exon 1 of 13		XP_011542814.2
NRG1	XM_017013367.2	c.308_316delCGGCGGCGG	p.Ala103_Ala105del	disruptive_inframe_deletion	Exon 1 of 11		XP_016868856.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000520407.5	c.308_316delCGGCGGCGG	p.Ala103_Ala105del	disruptive_inframe_deletion	Exon 1 of 5	1		ENSP00000434640.1
NRG1	ENST00000650866.1	c.37+861_37+869delCGGCGGCGG		intron_variant	Intron 1 of 12			ENSP00000499045.1
NRG1	ENST00000652698.1	c.37+861_37+869delCGGCGGCGG		intron_variant	Intron 1 of 11			ENSP00000499008.1

Frequencies

GnomAD3 genomes AF: 0.00000679 AC: 1 AN: 147342 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 972768 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 458300

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000678 AC: 1 AN: 147444 Hom.: 0 Cov.: 32 AF XY: 0.0000139 AC XY: 1 AN XY: 71830

Gnomad4 AFR AF: 0.0000244

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs770519581; hg19: chr8-31497799;