rs2238798

chr22-20120206-G-Achr22-20120206-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001278639.2(RANBP1):c.383+1057G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,224 control chromosomes in the GnomAD database, including 2,218 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 0.13 (2218 hom., cov: 33)
• Consequence: RANBP1 NM_001278639.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.485

Genes affected

RANBP1 (HGNC:9847): (RAN binding protein 1) This gene encodes a protein that forms a complex with Ras-related nuclear protein (Ran) and metabolizes guanoside triphosphate (GTP). This complex participates in the regulation of the cell cycle by controlling transport of proteins and nucleic acids into the nucleus. There are multiple pseudogenes for this gene on chromosomes 9, 12, 17, and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RANBP1	NM_001278639.2	c.383+1057G>A		intron_variant		ENST00000430524.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RANBP1	ENST00000430524.6	c.383+1057G>A		intron_variant		3	NM_001278639.2	A2

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19770 AN: 152106 Hom.: 2212 Cov.: 33

Gnomad AFR AF: 0.0277

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.130 AC: 19785 AN: 152224 Hom.: 2218 Cov.: 33 AF XY: 0.139 AC XY: 10332 AN XY: 74424

Gnomad4 AFR AF: 0.0276

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.0804

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.133

Alfa AF: 0.134 Hom.: 804

Bravo AF: 0.134

Asia WGS AF: 0.343 AC: 1192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.39
Dann	Benign	0.22

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

Other links and lift over

dbSNP: rs2238798; hg19: chr22-20107729;