rs11253185

Variant names:

• chr10-5453194-A-G
• rs11253185
• NM_001047160.3:c.595-56A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-5453194-A-G
• chr10-5453194-A-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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.354
• Publications: 11 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=-0.85).
• 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.595-56A>G		intron	N/A	NP_001040625.1
	NET1	NM_005863.5		c.433-56A>G		intron	N/A	NP_005854.2
	NET1	NR_073040.1		n.681-56A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NET1	ENST00000355029.9	TSL:1 MANE Select	c.595-56A>G		intron	N/A	ENSP00000347134.4
	NET1	ENST00000380359.3	TSL:1	c.433-56A>G		intron	N/A	ENSP00000369717.3
	NET1	ENST00000449083.5	TSL:5	c.94-101A>G		intron	N/A	ENSP00000403101.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37642 AN: 151934 Hom.: 4939 Cov.: 32

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.: 11 AF XY: 0.272 AC XY: 119118 AN XY: 437346

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

GnomAD4 genome AF: 0.248 AC: 37654 AN: 152052 Hom.: 4940 Cov.: 32 AF XY: 0.246 AC XY: 18257 AN XY: 74316

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: 72 AN: 292

European-Non Finnish (NFE) AF: 0.286 AC: 19421 AN: 67972

Other (OTH) AF: 0.262 AC: 553 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.19
DANN	Benign	0.41
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11253185; hg19: chr10-5495157; COSMIC: COSV61790713; COSMIC: COSV61790713;