chr22-20125730-T-G

Variant names:

• chr22-20125730-T-G
• rs175162
• NM_001278639.2:c.670+294T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001278639.2(RANBP1):​c.670+294T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,174,684 control chromosomes in the GnomAD database, including 44,297 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 0.27 (5721 hom., cov: 34)
  • Exomes 𝑓: 0.27 (38576 hom.)
• Consequence: RANBP1 NM_001278639.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 7 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RANBP1	NM_001278639.2	c.670+294T>G		intron_variant	Intron 4 of 5	ENST00000430524.6	NP_001265568.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RANBP1	ENST00000430524.6	c.670+294T>G		intron_variant	Intron 4 of 5	3	NM_001278639.2	ENSP00000401564.2

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41279 AN: 152116 Hom.: 5717 Cov.: 34

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.287

GnomAD4 exome AF: 0.273 AC: 278768 AN: 1022448 Hom.: 38576 AF XY: 0.274 AC XY: 135820 AN XY: 496242

African (AFR) AF: 0.273 AC: 6065 AN: 22228

American (AMR) AF: 0.233 AC: 3417 AN: 14676

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 4357 AN: 13104

East Asian (EAS) AF: 0.159 AC: 3053 AN: 19256

South Asian (SAS) AF: 0.307 AC: 17873 AN: 58292

European-Finnish (FIN) AF: 0.298 AC: 4640 AN: 15594

Middle Eastern (MID) AF: 0.258 AC: 680 AN: 2640

European-Non Finnish (NFE) AF: 0.272 AC: 227738 AN: 836590

Other (OTH) AF: 0.273 AC: 10945 AN: 40068

GnomAD4 genome AF: 0.271 AC: 41310 AN: 152236 Hom.: 5721 Cov.: 34 AF XY: 0.272 AC XY: 20228 AN XY: 74430

African (AFR) AF: 0.280 AC: 11652 AN: 41558

American (AMR) AF: 0.239 AC: 3655 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1154 AN: 3470

East Asian (EAS) AF: 0.154 AC: 795 AN: 5176

South Asian (SAS) AF: 0.291 AC: 1404 AN: 4830

European-Finnish (FIN) AF: 0.301 AC: 3180 AN: 10578

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18513 AN: 68006

Other (OTH) AF: 0.285 AC: 603 AN: 2116

Alfa AF: 0.265 Hom.: 1549

Bravo AF: 0.268

Asia WGS AF: 0.217 AC: 754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.24
DANN	Benign	0.29
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs175162; hg19: chr22-20113253; COSMIC: COSV107391027; COSMIC: COSV107391027;