rs1462906

Positions:

• chr8-32039076-T-C

Variant summary

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

The NM_001159999.3(NRG1):​c.37+399645T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 152,156 control chromosomes in the GnomAD database, including 53,871 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 0.79 (53871 hom., cov: 32)
• Consequence: NRG1 NM_001159999.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.764

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRG1	NM_001159999.3	c.37+399645T>C		intron_variant			NP_001153471.1
NRG1	NM_001159995.3	c.37+399645T>C		intron_variant			NP_001153467.1
NRG1	NM_001160001.3	c.37+399645T>C		intron_variant			NP_001153473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000520407.5	c.745+398347T>C		intron_variant		1		ENSP00000434640.1
NRG1-IT1	ENST00000521463.5	n.253+9591T>C		intron_variant		1
NRG1	ENST00000523534.5	c.304+398347T>C		intron_variant		5		ENSP00000429067.1

Frequencies

GnomAD3 genomes AF: 0.793 AC: 120635 AN: 152038 Hom.: 53857 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.908

Gnomad ASJ AF: 0.935

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.955

Gnomad FIN AF: 0.979

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.976

Gnomad OTH AF: 0.825

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

GnomAD4 genome AF: 0.793 AC: 120678 AN: 152156 Hom.: 53871 Cov.: 32 AF XY: 0.800 AC XY: 59517 AN XY: 74380

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.908

Gnomad4 ASJ AF: 0.935

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.956

Gnomad4 FIN AF: 0.979

Gnomad4 NFE AF: 0.976

Gnomad4 OTH AF: 0.827

Alfa AF: 0.871 Hom.: 7758

Bravo AF: 0.767

Asia WGS AF: 0.932 AC: 3242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.8
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1462906; hg19: chr8-31896592;