8-31641892-C-T

Variant names:

• chr8-31641892-C-T
• rs7819063
• ENST00000520407.5:c.745+1163C>T

Variant summary

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

The ENST00000520407.5(NRG1):​c.745+1163C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 151,828 control chromosomes in the GnomAD database, including 4,737 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 0.24 (4737 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 7 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 Gene-Disease associations (from GenCC):

• schizophrenia 6

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_001159999.3	c.37+2461C>T		intron_variant	Intron 1 of 12		NP_001153471.1
NRG1	NM_001159995.3	c.37+2461C>T		intron_variant	Intron 1 of 11		NP_001153467.1
NRG1	NM_001160001.3	c.37+2461C>T		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+1163C>T		intron_variant	Intron 1 of 4	1		ENSP00000434640.1
NRG1	ENST00000523534.5	c.304+1163C>T		intron_variant	Intron 1 of 12	5		ENSP00000429067.1
NRG1	ENST00000650866.1	c.37+2461C>T		intron_variant	Intron 1 of 12			ENSP00000499045.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36125 AN: 151704 Hom.: 4736 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.0124

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.283

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.238 AC: 36145 AN: 151822 Hom.: 4737 Cov.: 32 AF XY: 0.230 AC XY: 17069 AN XY: 74180

African (AFR) AF: 0.304 AC: 12586 AN: 41380

American (AMR) AF: 0.223 AC: 3400 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1045 AN: 3462

East Asian (EAS) AF: 0.0124 AC: 64 AN: 5156

South Asian (SAS) AF: 0.121 AC: 578 AN: 4776

European-Finnish (FIN) AF: 0.164 AC: 1730 AN: 10522

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15989 AN: 67958

Other (OTH) AF: 0.280 AC: 591 AN: 2112

Alfa AF: 0.236 Hom.: 5152

Bravo AF: 0.249

Asia WGS AF: 0.0840 AC: 290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.82
PhyloP100		1.4
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: rs7819063; hg19: chr8-31499408;