rs11932

Positions:

• chr3-122422288-C-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662

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]

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

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KPNA1	NM_002264.4	c.*4697G>A		3_prime_UTR_variant	14/14	ENST00000344337.11	NP_002255.3
WDR5B-DT	NR_125405.1	n.45+6038C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KPNA1	ENST00000344337.11	c.*4697G>A		3_prime_UTR_variant	14/14	1	NM_002264.4	ENSP00000343701	P1
WDR5B-DT	ENST00000609469.5	n.44+6038C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.154 AC: 22764 AN: 147838 Hom.: 1811 Cov.: 29

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: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.154 AC: 22787 AN: 147930 Hom.: 1820 Cov.: 29 AF XY: 0.153 AC XY: 10987 AN XY: 71742

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.0970

Gnomad4 ASJ AF: 0.0893

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.153

Alfa AF: 0.143 Hom.: 1845

Bravo AF: 0.153

Asia WGS AF: 0.225 AC: 784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs11932; hg19: chr3-122141135;