rs4881450

Positions:

• chr10-5447461-T-C

Variant summary

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

The NM_001047160.3(NET1):​c.256-4369T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 152,074 control chromosomes in the GnomAD database, including 38,223 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 0.71 (38223 hom., cov: 32)
• Consequence: NET1 NM_001047160.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210

Genes affected

NET1 (HGNC:14592): (neuroepithelial cell transforming 1) This gene is part of the family of Rho guanine nucleotide exchange factors. Members of this family activate Rho proteins by catalyzing the exchange of GDP for GTP. The protein encoded by this gene interacts with RhoA within the cell nucleus and may play a role in repairing DNA damage after ionizing radiation. Pseudogenes of this gene are located on the long arms of chromosomes 1, 7 and 18. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

NET1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NET1	NM_001047160.3	c.256-4369T>C		intron_variant		ENST00000355029.9	NP_001040625.1
NET1	NM_005863.5	c.93+603T>C		intron_variant			NP_005854.2
NET1	NR_073040.1	n.308+603T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NET1	ENST00000355029.9	c.256-4369T>C		intron_variant		1	NM_001047160.3	ENSP00000347134.4
NET1	ENST00000380359.3	c.93+603T>C		intron_variant		1		ENSP00000369717.3
NET1	ENST00000449083.5	c.93+603T>C		intron_variant		5		ENSP00000403101.1
NET1	ENST00000486354.1	n.250+603T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107351 AN: 151956 Hom.: 38189 Cov.: 32

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.710

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

GnomAD4 genome AF: 0.706 AC: 107440 AN: 152074 Hom.: 38223 Cov.: 32 AF XY: 0.710 AC XY: 52803 AN XY: 74358

Gnomad4 AFR AF: 0.654

Gnomad4 AMR AF: 0.761

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.824

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.718

Gnomad4 NFE AF: 0.714

Gnomad4 OTH AF: 0.708

Alfa AF: 0.634 Hom.: 2055

Bravo AF: 0.708

Asia WGS AF: 0.763 AC: 2653 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.6
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4881450; hg19: chr10-5489424;