Variant chr5-62474443-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_016338.5(IPO11):c.736C>T(p.Leu246Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000347 in 1,575,852 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 3 hom. )

Consequence

IPO11
NM_016338.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.57

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 5-62474443-C-T is Benign according to our data. Variant chr5-62474443-C-T is described in ClinVar as [Benign]. Clinvar id is 716114.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.57 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IPO11	NM_016338.5 linkuse as main transcript	c.736C>T	p.Leu246Leu	synonymous_variant	8/30	ENST00000325324.11	NP_057422.3	Q9UI26-1
IPO11	NM_001134779.2 linkuse as main transcript	c.856C>T	p.Leu286Leu	synonymous_variant	8/30		NP_001128251.1	Q9UI26-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IPO11	ENST00000325324.11 linkuse as main transcript	c.736C>T	p.Leu246Leu	synonymous_variant	8/30	1	NM_016338.5	ENSP00000316651.6	Q9UI26-1
IPO11	ENST00000424533.5 linkuse as main transcript	n.736C>T		non_coding_transcript_exon_variant	8/29	2		ENSP00000395685.1	F8WDV0
ENSG00000288643	ENST00000509663.2 linkuse as main transcript	n.65-40945C>T		intron_variant		3		ENSP00000502199.1	A0A6Q8PGD0

Frequencies

GnomAD3 genomes

AF:

0.00183

AC:

279

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00638

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.0000294

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000437

AC:

AN:

224304

Hom.:

AF XY:

0.000271

AC XY:

AN XY:

121914

show subpopulations

Gnomad AFR exome

AF:

0.00596

Gnomad AMR exome

AF:

0.000276

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000182

AC:

259

AN:

1423626

Hom.:

Cov.:

AF XY:

0.000145

AC XY:

103

AN XY:

708606

show subpopulations

Gnomad4 AFR exome

AF:

0.00675

Gnomad4 AMR exome

AF:

0.000342

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000547

Gnomad4 OTH exome

AF:

0.000459

GnomAD4 genome

AF:

0.00189

AC:

288

AN:

152226

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

132

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00657

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000982

Hom.:

Bravo

AF:

0.00232

Asia WGS

AF:

0.000867

AC:

AN:

3474

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

-0.26

CADD

Benign

9.2

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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