rs17236529

Variant names:

• chr3-160508519-C-T
• rs17236529
• NM_002268.5:c.1210-250G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002268.5(KPNA4):​c.1210-250G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0166 in 152,170 control chromosomes in the GnomAD database, including 35 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 0.017 (35 hom., cov: 32)
• Consequence: KPNA4 NM_002268.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.554
• Publications: 8 publications found

Genes affected

KPNA4 (HGNC:6397): (karyopherin subunit alpha 4) The nuclear import of karyophilic proteins is directed by short amino acid sequences termed nuclear localization signals (NLSs). Karyopherins, or importins, are cytoplasmic proteins that recognize NLSs and dock NLS-containing proteins to the nuclear pore complex. The protein encoded by this gene shares the sequence similarity with Xenopus importin-alpha and Saccharomyces cerevisiae Srp1. This protein is found to interact with the NLSs of DNA helicase Q1 and SV40 T antigen. [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=-0.87).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0166 (2530/152170) while in subpopulation NFE AF = 0.0269 (1831/67990). AF 95% confidence interval is 0.0259. There are 35 homozygotes in GnomAd4. There are 1213 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2530 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KPNA4	NM_002268.5	c.1210-250G>A		intron_variant	Intron 14 of 16	ENST00000334256.9	NP_002259.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KPNA4	ENST00000334256.9	c.1210-250G>A		intron_variant	Intron 14 of 16	1	NM_002268.5	ENSP00000334373.4

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 2531 AN: 152052 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.00490

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00702

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.0267

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0269

Gnomad OTH AF: 0.0130

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

GnomAD4 genome AF: 0.0166 AC: 2530 AN: 152170 Hom.: 35 Cov.: 32 AF XY: 0.0163 AC XY: 1213 AN XY: 74396

African (AFR) AF: 0.00489 AC: 203 AN: 41542

American (AMR) AF: 0.00701 AC: 107 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 55 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00497 AC: 24 AN: 4828

European-Finnish (FIN) AF: 0.0267 AC: 282 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0269 AC: 1831 AN: 67990

Other (OTH) AF: 0.0128 AC: 27 AN: 2106

Alfa AF: 0.0238 Hom.: 110

Bravo AF: 0.0145

Asia WGS AF: 0.00289 AC: 10 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.6
DANN	Benign	0.72
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs17236529; hg19: chr3-160226307;