chr5-170996530-C-T

Position:

• chr5-170996530-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RANBP17	NM_022897.5	c.1710+28153C>T		intron_variant		ENST00000523189.6	NP_075048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RANBP17	ENST00000523189.6	c.1710+28153C>T		intron_variant		1	NM_022897.5	ENSP00000427975	P1

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

Gnomad4 AFR AF: 0.648

Gnomad4 AMR AF: 0.682

Gnomad4 ASJ AF: 0.684

Gnomad4 EAS AF: 0.773

Gnomad4 SAS AF: 0.891

Gnomad4 FIN AF: 0.645

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.680

Alfa AF: 0.677 Hom.: 6821

Bravo AF: 0.678

Asia WGS AF: 0.766 AC: 2657 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.9
DANN	Benign	0.54

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: rs12716267; hg19: chr5-170423534; COSMIC: COSV66647240;