rs11253185

chr10-5453194-A-Gchr10-5453194-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	UniProt
NET1	NM_001047160.3	c.595-56A>G		intron_variant		ENST00000355029.9
NET1	NM_005863.5	c.433-56A>G		intron_variant
NET1	NR_073040.1	n.681-56A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NET1	ENST00000355029.9	c.595-56A>G		intron_variant		1	NM_001047160.3
NET1	ENST00000380359.3	c.433-56A>G		intron_variant		1		P1
NET1	ENST00000449083.5	c.94-101A>G		intron_variant		5
NET1	ENST00000465087.1			downstream_gene_variant		3

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

Gnomad4 AFR exome AF: 0.185

Gnomad4 AMR exome AF: 0.171

Gnomad4 ASJ exome AF: 0.317

Gnomad4 EAS exome AF: 0.192

Gnomad4 SAS exome AF: 0.261

Gnomad4 FIN exome AF: 0.282

Gnomad4 NFE exome AF: 0.286

Gnomad4 OTH exome AF: 0.267

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

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.262

Alfa AF: 0.280 Hom.: 10330

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
Dann	Benign	0.41

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

LitVar

Other links and lift over

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