rs10503898

Variant names:

• chr8-32086200-A-G
• rs10503898
• ENST00000520407.5:c.745+445471A>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+445471A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0602 in 152,280 control chromosomes in the GnomAD database, including 813 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 0.060 (813 hom., cov: 33)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302
• Publications: 0 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-IT1 (HGNC:43633): (NRG1 intronic transcript 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_001159999.3	c.37+446769A>G		intron_variant	Intron 1 of 12		NP_001153471.1
NRG1	NM_001159995.3	c.37+446769A>G		intron_variant	Intron 1 of 11		NP_001153467.1
NRG1	NM_001160001.3	c.37+446769A>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+445471A>G		intron_variant	Intron 1 of 4	1		ENSP00000434640.1
NRG1-IT1	ENST00000521463.6	n.254-12481A>G		intron_variant	Intron 2 of 3	1
NRG1	ENST00000523534.5	c.304+445471A>G		intron_variant	Intron 1 of 12	5		ENSP00000429067.1

Frequencies

GnomAD3 genomes AF: 0.0601 AC: 9151 AN: 152162 Hom.: 813 Cov.: 33

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0238

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.0779

Gnomad SAS AF: 0.0633

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000867

Gnomad OTH AF: 0.0550

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

GnomAD4 genome AF: 0.0602 AC: 9167 AN: 152280 Hom.: 813 Cov.: 33 AF XY: 0.0590 AC XY: 4391 AN XY: 74464

African (AFR) AF: 0.190 AC: 7911 AN: 41528

American (AMR) AF: 0.0238 AC: 364 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.0777 AC: 403 AN: 5188

South Asian (SAS) AF: 0.0631 AC: 305 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000867 AC: 59 AN: 68030

Other (OTH) AF: 0.0549 AC: 116 AN: 2114

Alfa AF: 0.0160 Hom.: 75

Bravo AF: 0.0668

Asia WGS AF: 0.0880 AC: 304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.81
PhyloP100		0.30
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: rs10503898; hg19: chr8-31943716;