chr8-31967616-A-G

Variant names:

• chr8-31967616-A-G
• rs1023911
• ENST00000520407.5:c.745+326887A>G

Variant summary

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

The ENST00000520407.5(NRG1):​c.745+326887A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 152,084 control chromosomes in the GnomAD database, including 34,543 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 0.63 (34543 hom., cov: 32)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233
• Publications: 5 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_001159999.3	c.37+328185A>G		intron_variant	Intron 1 of 12		NP_001153471.1
NRG1	NM_001159995.3	c.37+328185A>G		intron_variant	Intron 1 of 11		NP_001153467.1
NRG1	NM_001160001.3	c.37+328185A>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.745+326887A>G		intron_variant	Intron 1 of 4	1		ENSP00000434640.1
NRG1	ENST00000523534.5	c.304+326887A>G		intron_variant	Intron 1 of 12	5		ENSP00000429067.1
NRG1	ENST00000650866.1	c.37+328185A>G		intron_variant	Intron 1 of 12			ENSP00000499045.1

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95668 AN: 151966 Hom.: 34523 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.817

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.629 AC: 95712 AN: 152084 Hom.: 34543 Cov.: 32 AF XY: 0.630 AC XY: 46870 AN XY: 74338

African (AFR) AF: 0.262 AC: 10858 AN: 41464

American (AMR) AF: 0.712 AC: 10872 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2641 AN: 3472

East Asian (EAS) AF: 0.374 AC: 1932 AN: 5162

South Asian (SAS) AF: 0.711 AC: 3426 AN: 4816

European-Finnish (FIN) AF: 0.806 AC: 8534 AN: 10586

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.810 AC: 55098 AN: 67988

Other (OTH) AF: 0.660 AC: 1392 AN: 2110

Alfa AF: 0.753 Hom.: 24176

Bravo AF: 0.603

Asia WGS AF: 0.582 AC: 2022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.78
PhyloP100		-0.23
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: rs1023911; hg19: chr8-31825132;