5-170996530-C-T

Variant names:

• chr5-170996530-C-T
• rs12716267
• NM_022897.5:c.1710+28153C>T

Variant summary

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

The NM_022897.5(RANBP17):​c.1710+28153C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 151,980 control chromosomes in the GnomAD database, including 35,570 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 0.68 (35570 hom., cov: 32)
• Consequence: RANBP17 NM_022897.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161
• Publications: 4 publications found

Genes affected

RANBP17 (HGNC:14428): (RAN binding protein 17) The transport of protein and large RNAs through the nuclear pore complexes (NPC) is an energy-dependent and regulated process. The import of proteins with a nuclear localization signal (NLS) is accomplished by recognition of one or more clusters of basic amino acids by the importin-alpha/beta complex; see MIM 600685 and MIM 602738. The small GTPase RAN (MIM 601179) plays a key role in NLS-dependent protein import. RAN-binding protein-17 is a member of the importin-beta superfamily of nuclear transport receptors.[supplied by OMIM, Jul 2002]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022897.5. 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
	RANBP17	NM_022897.5	MANE Select	c.1710+28153C>T		intron	N/A	NP_075048.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RANBP17	ENST00000523189.6	TSL:1 MANE Select	c.1710+28153C>T		intron	N/A	ENSP00000427975.1
	RANBP17	ENST00000389118.8	TSL:2	n.1710+28153C>T		intron	N/A	ENSP00000373770.4
	RANBP17	ENST00000518492.1	TSL:2	n.120+28153C>T		intron	N/A	ENSP00000427980.1

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103609 AN: 151862 Hom.: 35543 Cov.: 32

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.891

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.688

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

GnomAD4 genome AF: 0.682 AC: 103678 AN: 151980 Hom.: 35570 Cov.: 32 AF XY: 0.687 AC XY: 51042 AN XY: 74288

African (AFR) AF: 0.648 AC: 26865 AN: 41428

American (AMR) AF: 0.682 AC: 10416 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2373 AN: 3468

East Asian (EAS) AF: 0.773 AC: 3988 AN: 5158

South Asian (SAS) AF: 0.891 AC: 4298 AN: 4824

European-Finnish (FIN) AF: 0.645 AC: 6807 AN: 10556

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46553 AN: 67960

Other (OTH) AF: 0.680 AC: 1435 AN: 2110

Alfa AF: 0.676 Hom.: 6985

Bravo AF: 0.678

Asia WGS AF: 0.766 AC: 2657 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.9
DANN	Benign	0.54
PhyloP100		0.16
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: rs12716267; hg19: chr5-170423534; COSMIC: COSV66647240;