8-32110442-T-C

Variant names:

• chr8-32110442-T-C
• rs1481757
• ENST00000520407.5:c.745+469713T>C

Variant summary

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

The ENST00000520407.5(NRG1):​c.745+469713T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 151,968 control chromosomes in the GnomAD database, including 39,787 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 0.72 (39787 hom., cov: 31)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.85
• Publications: 1 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-IT1 (HGNC:43633): (NRG1 intronic transcript 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_001159999.3	c.37+471011T>C		intron_variant	Intron 1 of 12		NP_001153471.1
NRG1	NM_001159995.3	c.37+471011T>C		intron_variant	Intron 1 of 11		NP_001153467.1
NRG1	NM_001160001.3	c.37+471011T>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.745+469713T>C		intron_variant	Intron 1 of 4	1		ENSP00000434640.1
NRG1	ENST00000523534.5	c.304+469713T>C		intron_variant	Intron 1 of 12	5		ENSP00000429067.1
NRG1	ENST00000650866.1	c.37+471011T>C		intron_variant	Intron 1 of 12			ENSP00000499045.1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109397 AN: 151850 Hom.: 39755 Cov.: 31

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.708

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

GnomAD4 genome AF: 0.720 AC: 109480 AN: 151968 Hom.: 39787 Cov.: 31 AF XY: 0.720 AC XY: 53465 AN XY: 74256

African (AFR) AF: 0.777 AC: 32197 AN: 41460

American (AMR) AF: 0.796 AC: 12157 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2186 AN: 3470

East Asian (EAS) AF: 0.488 AC: 2505 AN: 5138

South Asian (SAS) AF: 0.690 AC: 3324 AN: 4816

European-Finnish (FIN) AF: 0.698 AC: 7375 AN: 10564

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.700 AC: 47570 AN: 67930

Other (OTH) AF: 0.710 AC: 1497 AN: 2108

Alfa AF: 0.679 Hom.: 3653

Bravo AF: 0.729

Asia WGS AF: 0.614 AC: 2137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.031
DANN	Benign	0.36
PhyloP100		-2.8
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: rs1481757; hg19: chr8-31967958; COSMIC: COSV72974784;