8-32553981-G-C

Position:

• chr8-32553981-G-C

Variant summary

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

The NM_013964.5(NRG1):​c.100+5155G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 151,894 control chromosomes in the GnomAD database, including 12,739 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 0.39 (12739 hom., cov: 32)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRG1	NM_013964.5	c.100+5155G>C		intron_variant		ENST00000405005.8	NP_039258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000405005.8	c.100+5155G>C		intron_variant		1	NM_013964.5	ENSP00000384620	A2

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59517 AN: 151778 Hom.: 12732 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.392 AC: 59548 AN: 151894 Hom.: 12739 Cov.: 32 AF XY: 0.395 AC XY: 29330 AN XY: 74210

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.558

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.388

Alfa AF: 0.294 Hom.: 828

Bravo AF: 0.379

Asia WGS AF: 0.341 AC: 1185 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.094
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7835688; hg19: chr8-32411499;