rs4910052

Variant names:

• chr11-9433827-T-C
• rs4910052
• NM_006391.3:c.2055T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006391.3(IPO7):​c.2055T>C​(p.Asp685Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0662 in 1,610,730 control chromosomes in the GnomAD database, including 4,074 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 0.048 (243 hom., cov: 31)
  • Exomes 𝑓: 0.068 (3831 hom.)
• Consequence: IPO7 NM_006391.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84
• Publications: 10 publications found

Genes affected

IPO7 (HGNC:9852): (importin 7) The importin-alpha/beta complex and the GTPase Ran mediate nuclear import of proteins with a classical nuclear localization signal. The protein encoded by this gene is a member of a class of approximately 20 potential Ran targets that share a sequence motif related to the Ran-binding site of importin-beta. Similar to importin-beta, this protein prevents the activation of Ran's GTPase by RanGAP1 and inhibits nucleotide exchange on RanGTP, and also binds directly to nuclear pore complexes where it competes for binding sites with importin-beta and transportin. This protein has a Ran-dependent transport cycle and it can cross the nuclear envelope rapidly and in both directions. At least four importin beta-like transport receptors, namely importin beta itself, transportin, RanBP5 and RanBP7, directly bind and import ribosomal proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=1.84 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0713 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006391.3. 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
	IPO7	NM_006391.3	MANE Select	c.2055T>C	p.Asp685Asp	synonymous	Exon 18 of 25	NP_006382.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPO7	ENST00000379719.8	TSL:1 MANE Select	c.2055T>C	p.Asp685Asp	synonymous	Exon 18 of 25	ENSP00000369042.3

Frequencies

GnomAD3 genomes AF: 0.0478 AC: 7280 AN: 152150 Hom.: 243 Cov.: 31

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.0353

Gnomad ASJ AF: 0.0654

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0783

Gnomad FIN AF: 0.0531

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.0713

Gnomad OTH AF: 0.0421

GnomAD2 exomes AF: 0.0546 AC: 13681 AN: 250658 AF XY: 0.0587

Gnomad AFR exome AF: 0.0116

Gnomad AMR exome AF: 0.0229

Gnomad ASJ exome AF: 0.0646

Gnomad EAS exome AF: 0.000326

Gnomad FIN exome AF: 0.0530

Gnomad NFE exome AF: 0.0706

Gnomad OTH exome AF: 0.0598

GnomAD4 exome AF: 0.0681 AC: 99286 AN: 1458462 Hom.: 3831 Cov.: 32 AF XY: 0.0685 AC XY: 49737 AN XY: 725634

African (AFR) AF: 0.0103 AC: 345 AN: 33406

American (AMR) AF: 0.0241 AC: 1079 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0643 AC: 1680 AN: 26124

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39696

South Asian (SAS) AF: 0.0828 AC: 7130 AN: 86148

European-Finnish (FIN) AF: 0.0528 AC: 2779 AN: 52610

Middle Eastern (MID) AF: 0.0423 AC: 175 AN: 4136

European-Non Finnish (NFE) AF: 0.0742 AC: 82505 AN: 1111444

Other (OTH) AF: 0.0596 AC: 3585 AN: 60188

GnomAD4 genome AF: 0.0478 AC: 7277 AN: 152268 Hom.: 243 Cov.: 31 AF XY: 0.0471 AC XY: 3508 AN XY: 74450

African (AFR) AF: 0.0129 AC: 538 AN: 41570

American (AMR) AF: 0.0352 AC: 538 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0654 AC: 227 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.0778 AC: 375 AN: 4822

European-Finnish (FIN) AF: 0.0531 AC: 563 AN: 10612

Middle Eastern (MID) AF: 0.0240 AC: 7 AN: 292

European-Non Finnish (NFE) AF: 0.0713 AC: 4851 AN: 68008

Other (OTH) AF: 0.0421 AC: 89 AN: 2114

Alfa AF: 0.0592 Hom.: 226

Bravo AF: 0.0432

Asia WGS AF: 0.0230 AC: 82 AN: 3478

EpiCase AF: 0.0687

EpiControl AF: 0.0615

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.7
DANN	Benign	0.75
PhyloP100		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4910052; hg19: chr11-9455374;