8-32544043-T-C

Variant names:

• chr8-32544043-T-C
• rs6468119
• ENST00000520407.5:c.746-51785T>C

Variant summary

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

The NM_001159999.3(NRG1):​c.38-51785T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 152,020 control chromosomes in the GnomAD database, including 24,637 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 (24637 hom., cov: 32)
• Consequence: NRG1 NM_001159999.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870

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=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_001159999.3	c.38-51785T>C		intron_variant	Intron 1 of 12		NP_001153471.1
NRG1	NM_001159995.3	c.38-51785T>C		intron_variant	Intron 1 of 11		NP_001153467.1
NRG1	NM_001160001.3	c.38-51785T>C		intron_variant	Intron 1 of 10		NP_001153473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000520407.5	c.746-51785T>C		intron_variant	Intron 1 of 4	1		ENSP00000434640.1
NRG1	ENST00000523534.5	c.305-51785T>C		intron_variant	Intron 1 of 12	5		ENSP00000429067.1
NRG1	ENST00000650866.1	c.38-51785T>C		intron_variant	Intron 1 of 12			ENSP00000499045.1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85722 AN: 151902 Hom.: 24616 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.564 AC: 85780 AN: 152020 Hom.: 24637 Cov.: 32 AF XY: 0.569 AC XY: 42274 AN XY: 74306

Gnomad4 AFR AF: 0.470

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.811

Gnomad4 SAS AF: 0.561

Gnomad4 FIN AF: 0.647

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.555

Alfa AF: 0.574 Hom.: 41827

Bravo AF: 0.564

Asia WGS AF: 0.660 AC: 2294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.9
DANN	Benign	0.92

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6468119; hg19: chr8-32401561;