8-31775931-G-T

Variant names:

• chr8-31775931-G-T
• rs10503887
• ENST00000520407.5:c.745+135202G>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+135202G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 149,864 control chromosomes in the GnomAD database, including 2,428 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 0.16 (2428 hom., cov: 30)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_001159999.3	c.37+136500G>T		intron_variant	Intron 1 of 12		NP_001153471.1
NRG1	NM_001159995.3	c.37+136500G>T		intron_variant	Intron 1 of 11		NP_001153467.1
NRG1	NM_001160001.3	c.37+136500G>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+135202G>T		intron_variant	Intron 1 of 4	1		ENSP00000434640.1
NRG1	ENST00000523534.5	c.304+135202G>T		intron_variant	Intron 1 of 12	5		ENSP00000429067.1
NRG1	ENST00000650866.1	c.37+136500G>T		intron_variant	Intron 1 of 12			ENSP00000499045.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23255 AN: 149766 Hom.: 2429 Cov.: 30

Gnomad AFR AF: 0.0450

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.00566

Gnomad SAS AF: 0.0915

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.155 AC: 23256 AN: 149864 Hom.: 2428 Cov.: 30 AF XY: 0.149 AC XY: 10894 AN XY: 73034

African (AFR) AF: 0.0448 AC: 1826 AN: 40742

American (AMR) AF: 0.179 AC: 2695 AN: 15022

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 809 AN: 3464

East Asian (EAS) AF: 0.00568 AC: 29 AN: 5110

South Asian (SAS) AF: 0.0929 AC: 442 AN: 4760

European-Finnish (FIN) AF: 0.156 AC: 1535 AN: 9864

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.228 AC: 15384 AN: 67612

Other (OTH) AF: 0.188 AC: 392 AN: 2090

Alfa AF: 0.205 Hom.: 12724

Bravo AF: 0.154

Asia WGS AF: 0.0520 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.39
PhyloP100		0.22
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: rs10503887; hg19: chr8-31633447;