rs4239162

Variant names:

• chr17-47678444-G-A
• rs4239162
• NM_002265.6:c.2353+31G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002265.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KPNB1	NM_002265.6	MANE Select	c.2353+31G>A		intron	N/A	NP_002256.2
	KPNB1	NM_001276453.2		c.1918+31G>A		intron	N/A	NP_001263382.1	Q14974-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KPNB1	ENST00000290158.9	TSL:1 MANE Select	c.2353+31G>A		intron	N/A	ENSP00000290158.3	Q14974-1
	KPNB1	ENST00000931903.1		c.2503+31G>A		intron	N/A	ENSP00000601962.1
	KPNB1	ENST00000583648.6	TSL:4	c.2353+31G>A		intron	N/A	ENSP00000464042.2	Q14974-1

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

GnomAD2 exomes AF: 0.480 AC: 118389 AN: 246752 AF XY: 0.480

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 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

African (AFR) AF: 0.604 AC: 18793 AN: 31118

American (AMR) AF: 0.419 AC: 18512 AN: 44166

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 12855 AN: 25472

East Asian (EAS) AF: 0.462 AC: 18043 AN: 39068

South Asian (SAS) AF: 0.474 AC: 39674 AN: 83718

European-Finnish (FIN) AF: 0.466 AC: 24768 AN: 53108

Middle Eastern (MID) AF: 0.458 AC: 2259 AN: 4934

European-Non Finnish (NFE) AF: 0.495 AC: 499021 AN: 1008056

Other (OTH) AF: 0.497 AC: 27972 AN: 56334

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

African (AFR) AF: 0.607 AC: 25156 AN: 41450

American (AMR) AF: 0.459 AC: 7010 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1837 AN: 3468

East Asian (EAS) AF: 0.452 AC: 2334 AN: 5162

South Asian (SAS) AF: 0.456 AC: 2195 AN: 4816

European-Finnish (FIN) AF: 0.466 AC: 4921 AN: 10552

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.492 AC: 33455 AN: 67936

Other (OTH) AF: 0.505 AC: 1066 AN: 2110

Alfa AF: 0.502 Hom.: 9640

Bravo AF: 0.520

Asia WGS AF: 0.404 AC: 1405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.71
DANN	Benign	0.58
PhyloP100		-1.9
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

Other links and lift over

dbSNP: rs4239162; hg19: chr17-45755810;