rs9297145

Positions:

• chr7-99161494-C-A
• chr7-99161494-C-G
• chr7-99161494-C-T

Variant summary

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

The XM_017012211.2(KPNA7):​c.1546-15178G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 152,014 control chromosomes in the GnomAD database, including 35,431 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 0.67 (35431 hom., cov: 32)
• Consequence: KPNA7 XM_017012211.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.950

Genes affected

KPNA7 (HGNC:21839): (karyopherin subunit alpha 7) 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, but exhibits different nuclear localization signal binding specificity compared to other members of the family. A pseudogene of this gene has been defined on chromosome 5. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KPNA7	XM_017012211.2	c.1546-15178G>T		intron_variant			XP_016867700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102000 AN: 151896 Hom.: 35411 Cov.: 32

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.671 AC: 102067 AN: 152014 Hom.: 35431 Cov.: 32 AF XY: 0.675 AC XY: 50181 AN XY: 74300

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.734

Gnomad4 ASJ AF: 0.705

Gnomad4 EAS AF: 0.901

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.791

Gnomad4 NFE AF: 0.734

Gnomad4 OTH AF: 0.657

Alfa AF: 0.724 Hom.: 81432

Bravo AF: 0.662

Asia WGS AF: 0.708 AC: 2465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.4
DANN	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9297145; hg19: chr7-98759117;