5-62470318-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_016338.5(IPO11):c.708+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,611,942 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (40 hom.)
• Consequence: IPO11 NM_016338.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.21

Genes affected

IPO11 (HGNC:20628): (importin 11) Importins, including IPO11, are a members of the karyopherin/importin-beta family of transport receptors (see KPNB1; 602738) that mediate nucleocytoplasmic transport of protein and RNA cargoes (Plafker and Macara, 2000 [PubMed 11032817]).[supplied by OMIM, Sep 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-62470318-C-T is Benign according to our data. Variant chr5-62470318-C-T is described in ClinVar as [Benign]. Clinvar id is 769651.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00202 (308/152256) while in subpopulation EAS AF= 0.0316 (164/5186). AF 95% confidence interval is 0.0277. There are 7 homozygotes in gnomad4. There are 165 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IPO11	NM_016338.5	c.708+10C>T		intron_variant		ENST00000325324.11
IPO11	NM_001134779.2	c.828+10C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IPO11	ENST00000325324.11	c.708+10C>T		intron_variant		1	NM_016338.5	P1
IPO11	ENST00000409296.7	c.828+10C>T		intron_variant		2
IPO11	ENST00000424533.5	c.708+10C>T		intron_variant, NMD_transcript_variant		2
IPO11	ENST00000507640.1	n.119+10C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00202 AC: 307 AN: 152138 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00864

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0316

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00381 AC: 956 AN: 250912 Hom.: 9 AF XY: 0.00307 AC XY: 416 AN XY: 135620

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.0136

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0251

Gnomad SAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00167 AC: 2432 AN: 1459686 Hom.: 40 Cov.: 29 AF XY: 0.00152 AC XY: 1106 AN XY: 726246

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.0129

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0431

Gnomad4 SAS exome AF: 0.0000813

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000279

Gnomad4 OTH exome AF: 0.00169

GnomAD4 genome AF: 0.00202 AC: 308 AN: 152256 Hom.: 7 Cov.: 32 AF XY: 0.00222 AC XY: 165 AN XY: 74440

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.00863

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0316

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.000253 Hom.: 0

Bravo AF: 0.00263

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	13
Dann	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs117679224; hg19: chr5-61766145; COSMIC: COSV57578360; COSMIC: COSV57578360;