chr10-5447461-T-C

Variant names:

• chr10-5447461-T-C
• rs4881450
• NM_001047160.3:c.256-4369T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

ENSG00000288922 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001047160.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NET1	NM_001047160.3	MANE Select	c.256-4369T>C		intron	N/A	NP_001040625.1
	NET1	NM_005863.5		c.93+603T>C		intron	N/A	NP_005854.2
	NET1	NR_073040.1		n.308+603T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NET1	ENST00000355029.9	TSL:1 MANE Select	c.256-4369T>C		intron	N/A	ENSP00000347134.4
	NET1	ENST00000380359.3	TSL:1	c.93+603T>C		intron	N/A	ENSP00000369717.3
	NET1	ENST00000449083.5	TSL:5	c.93+603T>C		intron	N/A	ENSP00000403101.1

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

African (AFR) AF: 0.654 AC: 27117 AN: 41448

American (AMR) AF: 0.761 AC: 11637 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2372 AN: 3472

East Asian (EAS) AF: 0.824 AC: 4270 AN: 5184

South Asian (SAS) AF: 0.746 AC: 3591 AN: 4816

European-Finnish (FIN) AF: 0.718 AC: 7584 AN: 10570

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.714 AC: 48539 AN: 67976

Other (OTH) AF: 0.708 AC: 1497 AN: 2114

Alfa AF: 0.638 Hom.: 2245

Bravo AF: 0.708

Asia WGS AF: 0.763 AC: 2653 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.6
DANN	Benign	0.69
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4881450; hg19: chr10-5489424;