Variant chr5-62451753-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_016338.5(IPO11):c.336C>G(p.Leu112Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,614,056 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0091 ( 20 hom., cov: 32)

Exomes 𝑓: 0.00090 ( 23 hom. )

Consequence

IPO11
NM_016338.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.27

Variant links:

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]

IPO11 links:

ENSG00000288643 (HGNC:):

ENSG00000288643 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 5-62451753-C-G is Benign according to our data. Variant chr5-62451753-C-G is described in ClinVar as [Benign]. Clinvar id is 768002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.27 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00913 (1390/152250) while in subpopulation AFR AF= 0.0316 (1311/41548). AF 95% confidence interval is 0.0301. There are 20 homozygotes in gnomad4. There are 653 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IPO11	NM_016338.5 link	c.336C>G	p.Leu112Leu	synonymous_variant	5/30	ENST00000325324.11	NP_057422.3	Q9UI26-1
IPO11	NM_001134779.2 link	c.456C>G	p.Leu152Leu	synonymous_variant	5/30		NP_001128251.1	Q9UI26-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IPO11	ENST00000325324.11 link	c.336C>G	p.Leu112Leu	synonymous_variant	5/30	1	NM_016338.5	ENSP00000316651.6	Q9UI26-1
IPO11	ENST00000424533.5 link	n.336C>G		non_coding_transcript_exon_variant	5/29	2		ENSP00000395685.1	F8WDV0
ENSG00000288643	ENST00000509663.2 link	n.65-63635C>G		intron_variant		3		ENSP00000502199.1	A0A6Q8PGD0

Frequencies

GnomAD3 genomes

AF:

0.00909

AC:

1383

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0315

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00955

GnomAD3 exomes

AF:

0.00224

AC:

562

AN:

251334

Hom.:

AF XY:

0.00152

AC XY:

206

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.0317

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000897

AC:

1311

AN:

1461806

Hom.:

Cov.:

AF XY:

0.000726

AC XY:

528

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.0324

Gnomad4 AMR exome

AF:

0.00177

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.00204

GnomAD4 genome

AF:

0.00913

AC:

1390

AN:

152250

Hom.:

Cov.:

AF XY:

0.00877

AC XY:

653

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0316

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00945

Alfa

AF:

0.00251

Hom.:

Bravo

AF:

0.0107

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 01, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

4.1

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over