rs12114401

chr8-32398345-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000520407.5(NRG1):c.746-197483T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,608 control chromosomes in the GnomAD database, including 10,277 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 0.36 (10277 hom., cov: 30)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG1	NM_001159995.3	c.38-197483T>C		intron_variant
NRG1	NM_001159999.3	c.38-197483T>C		intron_variant
NRG1	NM_001160001.3	c.38-197483T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1	ENST00000520407.5	c.746-197483T>C		intron_variant		1
NRG1	ENST00000519301.6	c.38-197483T>C		intron_variant		5
NRG1	ENST00000523534.5	c.305-197483T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54287 AN: 151490 Hom.: 10263 Cov.: 30

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.00540

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.358 AC: 54332 AN: 151608 Hom.: 10277 Cov.: 30 AF XY: 0.352 AC XY: 26105 AN XY: 74068

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.00541

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.398

Alfa AF: 0.367 Hom.: 1805

Bravo AF: 0.363

Asia WGS AF: 0.157 AC: 550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	3.4
Dann	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12114401; hg19: chr8-32255861;