rs36048375

Positions:

• chr11-9441770-G-C

Variant summary

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

The NM_006391.3(IPO7):​c.2903-311G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0478 in 152,270 control chromosomes in the GnomAD database, including 242 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 (242 hom., cov: 32)
• Consequence: IPO7 NM_006391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IPO7	NM_006391.3	c.2903-311G>C		intron_variant		ENST00000379719.8	NP_006382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IPO7	ENST00000379719.8	c.2903-311G>C		intron_variant		1	NM_006391.3	ENSP00000369042	P1

Frequencies

GnomAD3 genomes AF: 0.0478 AC: 7279 AN: 152152 Hom.: 242 Cov.: 32

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.0949

Gnomad AMR AF: 0.0350

Gnomad ASJ AF: 0.0655

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0782

Gnomad FIN AF: 0.0530

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0713

Gnomad OTH AF: 0.0420

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

GnomAD4 genome AF: 0.0478 AC: 7276 AN: 152270 Hom.: 242 Cov.: 32 AF XY: 0.0471 AC XY: 3505 AN XY: 74446

Gnomad4 AFR AF: 0.0129

Gnomad4 AMR AF: 0.0349

Gnomad4 ASJ AF: 0.0655

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0776

Gnomad4 FIN AF: 0.0530

Gnomad4 NFE AF: 0.0713

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0564 Hom.: 37

Bravo AF: 0.0433

Asia WGS AF: 0.0250 AC: 88 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.61

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: rs36048375; hg19: chr11-9463317;