17-47624914-T-C

Variant names:

• chr17-47624914-T-C
• rs11079784
• ENST00000582066.2:n.262+11598A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000582066.2(KPNB1-DT):​n.262+11598A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 151,886 control chromosomes in the GnomAD database, including 16,719 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 0.46 (16719 hom., cov: 31)
• Consequence: KPNB1-DT ENST00000582066.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.441
• Publications: 35 publications found

Genes affected

KPNB1-DT (HGNC:55336): (KPNB1 divergent transcript)

NPEPPS (HGNC:7900): (aminopeptidase puromycin sensitive) This gene encodes the puromycin-sensitive aminopeptidase, a zinc metallopeptidase which hydrolyzes amino acids from the N-terminus of its substrate. The protein has been localized to both the cytoplasm and to cellular membranes. This enzyme degrades enkaphalins in the brain, and studies in mouse suggest that it is involved in proteolytic events regulating the cell cycle. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KPNB1-DT	NR_171699.1	n.205-848A>G		intron_variant	Intron 3 of 3
KPNB1-DT	NR_171700.1	n.204+1633A>G		intron_variant	Intron 3 of 3
KPNB1-DT	NR_171701.1	n.357+1633A>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KPNB1-DT	ENST00000582066.2	n.262+11598A>G		intron_variant	Intron 2 of 2	3
KPNB1-DT	ENST00000582389.6	n.313+1633A>G		intron_variant	Intron 3 of 3	5
KPNB1-DT	ENST00000584391.7	n.408+1633A>G		intron_variant	Intron 3 of 3	2

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69341 AN: 151768 Hom.: 16717 Cov.: 31

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.481

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.457 AC: 69371 AN: 151886 Hom.: 16719 Cov.: 31 AF XY: 0.463 AC XY: 34368 AN XY: 74224

African (AFR) AF: 0.301 AC: 12454 AN: 41420

American (AMR) AF: 0.534 AC: 8147 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1633 AN: 3472

East Asian (EAS) AF: 0.550 AC: 2839 AN: 5160

South Asian (SAS) AF: 0.559 AC: 2692 AN: 4812

European-Finnish (FIN) AF: 0.534 AC: 5613 AN: 10506

Middle Eastern (MID) AF: 0.555 AC: 162 AN: 292

European-Non Finnish (NFE) AF: 0.505 AC: 34297 AN: 67942

Other (OTH) AF: 0.482 AC: 1015 AN: 2104

Alfa AF: 0.493 Hom.: 18742

Bravo AF: 0.449

Asia WGS AF: 0.594 AC: 2066 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.4
DANN	Benign	0.66
PhyloP100		-0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11079784; hg19: chr17-45702280;