8-31948532-T-C

Position:

• chr8-31948532-T-C

Variant summary

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

The NM_001159999.3(NRG1):​c.37+309101T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 152,134 control chromosomes in the GnomAD database, including 62,306 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 0.90 (62306 hom., cov: 31)
• Consequence: NRG1 NM_001159999.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142

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=-0.62).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRG1	NM_001159999.3	c.37+309101T>C		intron_variant			NP_001153471.1
NRG1	NM_001159995.3	c.37+309101T>C		intron_variant			NP_001153467.1
NRG1	NM_001160001.3	c.37+309101T>C		intron_variant			NP_001153473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000520407.5	c.745+307803T>C		intron_variant		1		ENSP00000434640.1
NRG1	ENST00000523534.5	c.304+307803T>C		intron_variant		5		ENSP00000429067.1
NRG1	ENST00000650866.1	c.37+309101T>C		intron_variant				ENSP00000499045.1

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136677 AN: 152016 Hom.: 62237 Cov.: 31

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.861

Gnomad AMR AF: 0.877

Gnomad ASJ AF: 0.889

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.909

Gnomad OTH AF: 0.904

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

GnomAD4 genome AF: 0.899 AC: 136807 AN: 152134 Hom.: 62306 Cov.: 31 AF XY: 0.894 AC XY: 66439 AN XY: 74340

Gnomad4 AFR AF: 0.967

Gnomad4 AMR AF: 0.877

Gnomad4 ASJ AF: 0.889

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.835

Gnomad4 FIN AF: 0.879

Gnomad4 NFE AF: 0.909

Gnomad4 OTH AF: 0.904

Alfa AF: 0.906 Hom.: 24823

Bravo AF: 0.899

Asia WGS AF: 0.689 AC: 2396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs383632; hg19: chr8-31806048;