chr8-32542597-T-C

Position:

• chr8-32542597-T-C

Variant summary

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

The ENST00000520407.5(NRG1):​c.746-53231T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,928 control chromosomes in the GnomAD database, including 24,407 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 0.56 (24407 hom., cov: 32)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.428

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRG1	NM_001159995.3	c.38-53231T>C		intron_variant			NP_001153467.1
NRG1	NM_001159999.3	c.38-53231T>C		intron_variant			NP_001153471.1
NRG1	NM_001160001.3	c.38-53231T>C		intron_variant			NP_001153473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000520407.5	c.746-53231T>C		intron_variant		1		ENSP00000434640
NRG1	ENST00000519301.6	c.38-53231T>C		intron_variant		5		ENSP00000429582
NRG1	ENST00000523534.5	c.305-53231T>C		intron_variant		5		ENSP00000429067

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84925 AN: 151812 Hom.: 24396 Cov.: 32

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.559 AC: 84966 AN: 151928 Hom.: 24407 Cov.: 32 AF XY: 0.554 AC XY: 41135 AN XY: 74224

Gnomad4 AFR AF: 0.581

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.586

Gnomad4 OTH AF: 0.571

Alfa AF: 0.574 Hom.: 26359

Bravo AF: 0.551

Asia WGS AF: 0.370 AC: 1285 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	1.5
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7826312; hg19: chr8-32400115;