8-31640107-C-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Moderate BP7 BS2

The ENST00000520407.5(NRG1):c.123C>A(p.Thr41=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,150,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.000088 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: NRG1 ENST00000520407.5 synonymous
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.262

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 Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BP7: Synonymous conserved (PhyloP=0.262 with no splicing effect.
• BS2: High AC in GnomAd at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG1	NM_013962.3	c.123C>A	p.Thr41=	synonymous_variant	1/5
NRG1	XM_011544512.3	c.123C>A	p.Thr41=	synonymous_variant	1/13
NRG1	XM_017013367.2	c.123C>A	p.Thr41=	synonymous_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1	ENST00000520407.5	c.123C>A	p.Thr41=	synonymous_variant	1/5	1
NRG1	ENST00000519301.6	c.37+676C>A		intron_variant		5
NRG1	ENST00000650866.1	c.37+676C>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0000876 AC: 13 AN: 148444 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00195

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000450

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000220 AC: 22 AN: 1001638 Hom.: 0 Cov.: 34 AF XY: 0.0000294 AC XY: 14 AN XY: 475634

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000268

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000117

Gnomad4 NFE exome AF: 0.0000161

Gnomad4 OTH exome AF: 0.0000270

GnomAD4 genome AF: 0.0000875 AC: 13 AN: 148550 Hom.: 0 Cov.: 32 AF XY: 0.000110 AC XY: 8 AN XY: 72418

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00196

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000450

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000106

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

literature only

Psychiatry Genetics Yale University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
Cadd	Benign	18
Dann	Benign	0.97

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs367543154; hg19: chr8-31497623; COSMIC: COSV73060609; COSMIC: COSV73060609;