chr10-5448969-A-T

Variant names:

• chr10-5448969-A-T
• rs12570751
• NM_001047160.3:c.256-2861A>T

Variant summary

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

The NM_001047160.3(NET1):​c.256-2861A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 151,998 control chromosomes in the GnomAD database, including 5,720 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 0.27 (5720 hom., cov: 31)
• Consequence: NET1 NM_001047160.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.732
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 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.256-2861A>T		intron	N/A	NP_001040625.1
	NET1	NM_005863.5		c.93+2111A>T		intron	N/A	NP_005854.2
	NET1	NR_073040.1		n.308+2111A>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NET1	ENST00000355029.9	TSL:1 MANE Select	c.256-2861A>T		intron	N/A	ENSP00000347134.4
	NET1	ENST00000380359.3	TSL:1	c.93+2111A>T		intron	N/A	ENSP00000369717.3
	NET1	ENST00000449083.5	TSL:5	c.93+2111A>T		intron	N/A	ENSP00000403101.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41045 AN: 151880 Hom.: 5719 Cov.: 31

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.270 AC: 41065 AN: 151998 Hom.: 5720 Cov.: 31 AF XY: 0.267 AC XY: 19829 AN XY: 74262

African (AFR) AF: 0.265 AC: 10987 AN: 41442

American (AMR) AF: 0.229 AC: 3498 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1100 AN: 3466

East Asian (EAS) AF: 0.176 AC: 912 AN: 5170

South Asian (SAS) AF: 0.256 AC: 1230 AN: 4814

European-Finnish (FIN) AF: 0.281 AC: 2971 AN: 10558

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19410 AN: 67952

Other (OTH) AF: 0.277 AC: 585 AN: 2114

Alfa AF: 0.170 Hom.: 332

Bravo AF: 0.265

Asia WGS AF: 0.233 AC: 811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.37
DANN	Benign	0.45
PhyloP100		-0.73
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: rs12570751; hg19: chr10-5490932;