8-31640283-AGGCGGCGGC-AGGCGGCGGCGGCGGC

Variant names:

• chr8-31640283-A-AGGCGGC
• rs770519581
• ENST00000520407.5:c.311_316dupCGGCGG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_013962.3(NRG1):​c.311_316dupCGGCGG​(p.Ala104_Ala105dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 1,120,108 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 0.000034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: NRG1 NM_013962.3 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_013962.3	c.311_316dupCGGCGG	p.Ala104_Ala105dup	disruptive_inframe_insertion	Exon 1 of 5		NP_039256.2
NRG1	XM_011544512.3	c.311_316dupCGGCGG	p.Ala104_Ala105dup	disruptive_inframe_insertion	Exon 1 of 13		XP_011542814.2
NRG1	XM_017013367.2	c.311_316dupCGGCGG	p.Ala104_Ala105dup	disruptive_inframe_insertion	Exon 1 of 11		XP_016868856.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000520407.5	c.311_316dupCGGCGG	p.Ala104_Ala105dup	disruptive_inframe_insertion	Exon 1 of 5	1		ENSP00000434640.1
NRG1	ENST00000650866.1	c.37+864_37+869dupCGGCGG		intron_variant	Intron 1 of 12			ENSP00000499045.1
NRG1	ENST00000652698.1	c.37+864_37+869dupCGGCGG		intron_variant	Intron 1 of 11			ENSP00000499008.1

Frequencies

GnomAD3 genomes AF: 0.0000339 AC: 5 AN: 147342 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000734

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: 0.0000302

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000154 AC: 15 AN: 972766 Hom.: 0 Cov.: 34 AF XY: 0.0000175 AC XY: 8 AN XY: 458300

Gnomad4 AFR exome AF: 0.000159

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: 0.0000106

Gnomad4 OTH exome AF: 0.0000562

GnomAD4 genome AF: 0.0000339 AC: 5 AN: 147342 Hom.: 0 Cov.: 32 AF XY: 0.0000418 AC XY: 3 AN XY: 71716

Gnomad4 AFR AF: 0.0000734

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: 0.0000302

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000529

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;