chr17-47678444-G-A

Position:

• chr17-47678444-G-A

Variant summary

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

The NM_002265.6(KPNB1):​c.2353+31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 1,497,938 control chromosomes in the GnomAD database, including 184,211 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 0.52 (20731 hom., cov: 32)
  • Exomes 𝑓: 0.49 (163480 hom.)
• Consequence: KPNB1 NM_002265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

Genes affected

KPNB1 (HGNC:6400): (karyopherin subunit beta 1) Nucleocytoplasmic transport, a signal- and energy-dependent process, takes place through nuclear pore complexes embedded in the nuclear envelope. The import of proteins containing a nuclear localization signal (NLS) requires the NLS import receptor, a heterodimer of importin alpha and beta subunits also known as karyopherins. Importin alpha binds the NLS-containing cargo in the cytoplasm and importin beta docks the complex at the cytoplasmic side of the nuclear pore complex. In the presence of nucleoside triphosphates and the small GTP binding protein Ran, the complex moves into the nuclear pore complex and the importin subunits dissociate. Importin alpha enters the nucleoplasm with its passenger protein and importin beta remains at the pore. Interactions between importin beta and the FG repeats of nucleoporins are essential in translocation through the pore complex. The protein encoded by this gene is a member of the importin beta family. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2013]

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 (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KPNB1	NM_002265.6	c.2353+31G>A		intron_variant		ENST00000290158.9	NP_002256.2
KPNB1	NM_001276453.2	c.1918+31G>A		intron_variant			NP_001263382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KPNB1	ENST00000290158.9	c.2353+31G>A		intron_variant		1	NM_002265.6	ENSP00000290158	P1

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78405 AN: 151846 Hom.: 20698 Cov.: 32

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.506

GnomAD3 exomes AF: 0.480 AC: 118389 AN: 246752 Hom.: 28532 AF XY: 0.480 AC XY: 64080 AN XY: 133502

Gnomad AFR exome AF: 0.617

Gnomad AMR exome AF: 0.412

Gnomad ASJ exome AF: 0.505

Gnomad EAS exome AF: 0.454

Gnomad SAS exome AF: 0.478

Gnomad FIN exome AF: 0.464

Gnomad NFE exome AF: 0.487

Gnomad OTH exome AF: 0.473

GnomAD4 exome AF: 0.492 AC: 661897 AN: 1345974 Hom.: 163480 Cov.: 20 AF XY: 0.491 AC XY: 331960 AN XY: 675732

Gnomad4 AFR exome AF: 0.604

Gnomad4 AMR exome AF: 0.419

Gnomad4 ASJ exome AF: 0.505

Gnomad4 EAS exome AF: 0.462

Gnomad4 SAS exome AF: 0.474

Gnomad4 FIN exome AF: 0.466

Gnomad4 NFE exome AF: 0.495

Gnomad4 OTH exome AF: 0.497

GnomAD4 genome AF: 0.517 AC: 78499 AN: 151964 Hom.: 20731 Cov.: 32 AF XY: 0.512 AC XY: 38050 AN XY: 74270

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.505

Alfa AF: 0.510 Hom.: 4763

Bravo AF: 0.520

Asia WGS AF: 0.404 AC: 1405 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	0.71
DANN	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4239162; hg19: chr17-45755810;