Variant rs7958223 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000543796.6(RAN):c.435+20C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,585,404 control chromosomes in the GnomAD database, including 72,135 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 0.31 ( 7355 hom., cov: 33)

Exomes 𝑓: 0.30 ( 64780 hom. )

Consequence

RAN
ENST00000543796.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.17

Variant links:

Genes affected

RAN (HGNC:9846): (RAN, member RAS oncogene family) RAN (ras-related nuclear protein) is a small GTP binding protein belonging to the RAS superfamily that is essential for the translocation of RNA and proteins through the nuclear pore complex. The RAN protein is also involved in control of DNA synthesis and cell cycle progression. Nuclear localization of RAN requires the presence of regulator of chromosome condensation 1 (RCC1). Mutations in RAN disrupt DNA synthesis. Because of its many functions, it is likely that RAN interacts with several other proteins. RAN regulates formation and organization of the microtubule network independently of its role in the nucleus-cytosol exchange of macromolecules. RAN could be a key signaling molecule regulating microtubule polymerization during mitosis. RCC1 generates a high local concentration of RAN-GTP around chromatin which, in turn, induces the local nucleation of microtubules. RAN is an androgen receptor (AR) coactivator that binds differentially with different lengths of polyglutamine within the androgen receptor. Polyglutamine repeat expansion in the AR is linked to Kennedy's disease (X-linked spinal and bulbar muscular atrophy). RAN coactivation of the AR diminishes with polyglutamine expansion within the AR, and this weak coactivation may lead to partial androgen insensitivity during the development of Kennedy's disease. [provided by RefSeq, Jul 2008]

RAN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
RAN	NM_006325.5 linkuse as main transcript	c.435+20C>A	intron_variant	ENST00000543796.6	NP_006316.1
RAN	NM_001300796.2 linkuse as main transcript	c.171+20C>A	intron_variant		NP_001287725.1
RAN	NM_001300797.2 linkuse as main transcript	c.171+20C>A	intron_variant		NP_001287726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAN	ENST00000543796.6 linkuse as main transcript	c.435+20C>A		intron_variant		1	NM_006325.5	ENSP00000446215	P1

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47421

AN:

151946

Hom.:

7347

Cov.:

show subpopulations

Gnomad AFR

AF:

0.320

Gnomad AMI

AF:

0.313

Gnomad AMR

AF:

0.308

Gnomad ASJ

AF:

0.329

Gnomad EAS

AF:

0.213

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.390

Gnomad MID

AF:

0.264

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.302

GnomAD3 exomes

AF:

0.298

AC:

72742

AN:

244406

Hom.:

11077

AF XY:

0.294

AC XY:

38850

AN XY:

132268

show subpopulations

Gnomad AFR exome

AF:

0.321

Gnomad AMR exome

AF:

0.302

Gnomad ASJ exome

AF:

0.341

Gnomad EAS exome

AF:

0.207

Gnomad SAS exome

AF:

0.202

Gnomad FIN exome

AF:

0.371

Gnomad NFE exome

AF:

0.314

Gnomad OTH exome

AF:

0.315

GnomAD4 exome

AF:

0.299

AC:

428326

AN:

1433338

Hom.:

64780

Cov.:

AF XY:

0.296

AC XY:

211158

AN XY:

713126

show subpopulations

Gnomad4 AFR exome

AF:

0.318

Gnomad4 AMR exome

AF:

0.299

Gnomad4 ASJ exome

AF:

0.339

Gnomad4 EAS exome

AF:

0.247

Gnomad4 SAS exome

AF:

0.202

Gnomad4 FIN exome

AF:

0.364

Gnomad4 NFE exome

AF:

0.304

Gnomad4 OTH exome

AF:

0.293

GnomAD4 genome

AF:

0.312

AC:

47449

AN:

152066

Hom.:

7355

Cov.:

AF XY:

0.312

AC XY:

23208

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.320

Gnomad4 AMR

AF:

0.307

Gnomad4 ASJ

AF:

0.329

Gnomad4 EAS

AF:

0.213

Gnomad4 SAS

AF:

0.194

Gnomad4 FIN

AF:

0.390

Gnomad4 NFE

AF:

0.311

Gnomad4 OTH

AF:

0.301

Alfa

AF:

0.260

Hom.:

1214

Bravo

AF:

0.306

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.0040

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over