5-62474443-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_016338.5(IPO11):c.736C>T(p.Leu246=) 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.57

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 Likely_benign. Variant got -5 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_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.57 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IPO11	NM_016338.5	c.736C>T	p.Leu246=	synonymous_variant	8/30	ENST00000325324.11
IPO11	NM_001134779.2	c.856C>T	p.Leu286=	synonymous_variant	8/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IPO11	ENST00000325324.11	c.736C>T	p.Leu246=	synonymous_variant	8/30	1	NM_016338.5	P1
IPO11	ENST00000409296.7	c.856C>T	p.Leu286=	synonymous_variant	8/30	2
IPO11	ENST00000507640.1	n.147C>T		non_coding_transcript_exon_variant	3/4	3
IPO11	ENST00000424533.5	c.736C>T	p.Leu246=	synonymous_variant, NMD_transcript_variant	8/29	2

Frequencies

GnomAD3 genomes AF: 0.00183 AC: 279 AN: 152110 Hom.: 0 Cov.: 32

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: 98 AN: 224304 Hom.: 1 AF XY: 0.000271 AC XY: 33 AN XY: 121914

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.: 3 Cov.: 26 AF XY: 0.000145 AC XY: 103 AN XY: 708606

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.: 0 Cov.: 32 AF XY: 0.00177 AC XY: 132 AN XY: 74424

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.: 1

Bravo AF: 0.00232

Asia WGS AF: 0.000867 AC: 3 AN: 3474

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

Jun 01, 2018

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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

Other links and lift over

dbSNP: rs142408263; hg19: chr5-61770270;