dbSNP rs11253185: NET1:c.595-56A>G (chr10-5453194-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001047160.3(NET1):c.595-56A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 980,022 control chromosomes in the GnomAD database, including 36,428 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 0.25 ( 4940 hom., cov: 32)

Exomes 𝑓: 0.27 ( 31488 hom. )

Consequence

NET1
NM_001047160.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.354

Publications

11 publications found

Variant links:

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 links:

ENSG00000288922 (HGNC:):

ENSG00000288922 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NET1	NM_001047160.3 link	c.595-56A>G	intron_variant	Intron 6 of 11	ENST00000355029.9	NP_001040625.1	Q7Z628-1Q5SQI5
NET1	NM_005863.5 link	c.433-56A>G	intron_variant	Intron 4 of 9		NP_005854.2	Q7Z628-2Q5SQI7
NET1	NR_073040.1 link	n.681-56A>G	intron_variant	Intron 4 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NET1	ENST00000355029.9 link	c.595-56A>G		intron_variant	Intron 6 of 11	1	NM_001047160.3	ENSP00000347134.4		Q7Z628-1

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37642

AN:

151934

Hom.:

4939

Cov.:

show subpopulations

Gnomad AFR

AF:

0.186

Gnomad AMI

AF:

0.330

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.317

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.255

Gnomad FIN

AF:

0.282

Gnomad MID

AF:

0.245

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.260

GnomAD4 exome

AF:

0.271

AC:

224239

AN:

827970

Hom.:

31488

Cov.:

AF XY:

0.272

AC XY:

119118

AN XY:

437346

show subpopulations

African (AFR)

AF:

0.185

AC:

3918

AN:

21202

American (AMR)

AF:

0.171

AC:

7304

AN:

42658

Ashkenazi Jewish (ASJ)

AF:

0.317

AC:

6945

AN:

21906

East Asian (EAS)

AF:

0.192

AC:

7063

AN:

36858

South Asian (SAS)

AF:

0.261

AC:

18960

AN:

72674

European-Finnish (FIN)

AF:

0.282

AC:

14948

AN:

52926

Middle Eastern (MID)

AF:

0.291

AC:

1297

AN:

4456

European-Non Finnish (NFE)

AF:

0.286

AC:

153298

AN:

535908

Other (OTH)

AF:

0.267

AC:

10506

AN:

39382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

9024

18047

27071

36094

45118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.248

AC:

37654

AN:

152052

Hom.:

4940

Cov.:

AF XY:

0.246

AC XY:

18257

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.186

AC:

7713

AN:

41472

American (AMR)

AF:

0.221

AC:

3376

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.317

AC:

1100

AN:

3468

East Asian (EAS)

AF:

0.176

AC:

912

AN:

5182

South Asian (SAS)

AF:

0.256

AC:

1231

AN:

4816

European-Finnish (FIN)

AF:

0.282

AC:

2976

AN:

10548

Middle Eastern (MID)

AF:

0.247

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.286

AC:

19421

AN:

67972

Other (OTH)

AF:

0.262

AC:

553

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1406

2812

4219

5625

7031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.273

Hom.:

22679

Bravo

AF:

0.239

Asia WGS

AF:

0.225

AC:

783

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.19

(source)

DANN

Benign

0.41

PhyloP100

-0.35

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs11253185

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over