NM_013964.5:c.503-11884T>C

Variant names:

• chr8-32716065-T-C
• rs16879814
• NM_013964.5:c.503-11884T>C

Variant summary

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

The NM_013964.5(NRG1):​c.503-11884T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,060 control chromosomes in the GnomAD database, including 8,070 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 0.32 (8070 hom., cov: 32)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013964.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	NM_013964.5	MANE Select	c.503-11884T>C		intron	N/A	NP_039258.1	Q02297-1
	NRG1	NM_001322205.2		c.668-11884T>C		intron	N/A	NP_001309134.1	A0A494C0Q4
	NRG1	NM_013956.5		c.503-11884T>C		intron	N/A	NP_039250.2	Q02297-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	ENST00000405005.8	TSL:1 MANE Select	c.503-11884T>C		intron	N/A	ENSP00000384620.2	Q02297-1
	NRG1	ENST00000287842.7	TSL:1	c.503-11884T>C		intron	N/A	ENSP00000287842.4	Q02297-6
	NRG1	ENST00000356819.7	TSL:1	c.503-11884T>C		intron	N/A	ENSP00000349275.6	Q02297-7

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48271 AN: 151942 Hom.: 8069 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.0889

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.318 AC: 48284 AN: 152060 Hom.: 8070 Cov.: 32 AF XY: 0.319 AC XY: 23719 AN XY: 74334

African (AFR) AF: 0.257 AC: 10654 AN: 41488

American (AMR) AF: 0.300 AC: 4588 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1364 AN: 3470

East Asian (EAS) AF: 0.0891 AC: 460 AN: 5164

South Asian (SAS) AF: 0.252 AC: 1217 AN: 4820

European-Finnish (FIN) AF: 0.437 AC: 4612 AN: 10556

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24215 AN: 67974

Other (OTH) AF: 0.300 AC: 632 AN: 2106

Alfa AF: 0.341 Hom.: 15473

Bravo AF: 0.305

Asia WGS AF: 0.182 AC: 632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.51
PhyloP100		-0.35
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: rs16879814; hg19: chr8-32573583;