dbSNP rs11932: KPNA1:c.*4697G>A (chr3-122422288-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002264.4(KPNA1):c.*4697G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 147,930 control chromosomes in the GnomAD database, including 1,820 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 0.15 ( 1820 hom., cov: 29)

Failed GnomAD Quality Control

Consequence

KPNA1
NM_002264.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.662

Publications

12 publications found

Variant links:

Genes affected

KPNA1 (HGNC:6394): (karyopherin subunit alpha 1) The transport of molecules between the nucleus and the cytoplasm in eukaryotic cells is mediated by the nuclear pore complex (NPC), which consists of 60-100 proteins. Small molecules (up to 70 kD) can pass through the nuclear pore by nonselective diffusion while larger molecules are transported by an active process. The protein encoded by this gene belongs to the importin alpha family, and is involved in nuclear protein import. This protein interacts with the recombination activating gene 1 (RAG1) protein and is a putative substrate of the RAG1 ubiquitin ligase. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

KPNA1 links:

WDR5B-DT (HGNC:55192): (WDR5B divergent transcript)

WDR5B-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002264.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KPNA1	NM_002264.4	MANE Select	c.*4697G>A	3_prime_UTR	Exon 14 of 14	NP_002255.3
KPNA1	NR_026698.2		n.6625G>A	non_coding_transcript_exon	Exon 15 of 15
WDR5B-DT	NR_125405.1		n.45+6038C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KPNA1	ENST00000344337.11	TSL:1 MANE Select	c.*4697G>A	3_prime_UTR	Exon 14 of 14	ENSP00000343701.6
WDR5B-DT	ENST00000608015.1	TSL:5	n.27-3319C>T	intron	N/A
WDR5B-DT	ENST00000608346.2	TSL:2	n.48+6038C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

22764

AN:

147838

Hom.:

1811

Cov.:

show subpopulations

Gnomad AFR

AF:

0.179

Gnomad AMI

AF:

0.183

Gnomad AMR

AF:

0.0971

Gnomad ASJ

AF:

0.0893

Gnomad EAS

AF:

0.327

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.103

Gnomad NFE

AF:

0.145

Gnomad OTH

AF:

0.150

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.154

AC:

22787

AN:

147930

Hom.:

1820

Cov.:

AF XY:

0.153

AC XY:

10987

AN XY:

71742

show subpopulations

African (AFR)

AF:

0.179

AC:

7160

AN:

39950

American (AMR)

AF:

0.0970

AC:

1407

AN:

14510

Ashkenazi Jewish (ASJ)

AF:

0.0893

AC:

310

AN:

3470

East Asian (EAS)

AF:

0.327

AC:

1657

AN:

5068

South Asian (SAS)

AF:

0.108

AC:

504

AN:

4678

European-Finnish (FIN)

AF:

0.151

AC:

1432

AN:

9504

Middle Eastern (MID)

AF:

0.104

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.145

AC:

9811

AN:

67522

Other (OTH)

AF:

0.153

AC:

312

AN:

2044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

940

1880

2821

3761

4701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.152

Hom.:

5648

Bravo

AF:

0.153

Asia WGS

AF:

0.225

AC:

784

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.1

(source)

DANN

Benign

0.62

PhyloP100

-0.66

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over