XM_017012211.2:c.1545+15039C>T

Variant names:

• chr7-99162881-G-A
• rs7809799
• XM_017012211.2:c.1545+15039C>T

Variant summary

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

The XM_017012211.2(KPNA7):​c.1545+15039C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.923 in 151,534 control chromosomes in the GnomAD database, including 64,554 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 0.92 (64554 hom., cov: 32)
• Consequence: KPNA7 XM_017012211.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 28 publications found

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]

KPNA7 Gene-Disease associations (from GenCC):

• oocyte/zygote/embryo maturation arrest 17

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• partial corpus callosum agenesis-cerebellar vermis hypoplasia with posterior fossa cysts syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KPNA7	XM_017012211.2	c.1545+15039C>T		intron_variant	Intron 10 of 10		XP_016867700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.923 AC: 139691 AN: 151414 Hom.: 64507 Cov.: 32

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.947

Gnomad AMR AF: 0.949

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.947

Gnomad FIN AF: 0.956

Gnomad MID AF: 0.936

Gnomad NFE AF: 0.957

Gnomad OTH AF: 0.920

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

GnomAD4 genome AF: 0.923 AC: 139796 AN: 151534 Hom.: 64554 Cov.: 32 AF XY: 0.924 AC XY: 68476 AN XY: 74138

African (AFR) AF: 0.835 AC: 34098 AN: 40856

American (AMR) AF: 0.949 AC: 14482 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3152 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5187 AN: 5188

South Asian (SAS) AF: 0.947 AC: 4571 AN: 4826

European-Finnish (FIN) AF: 0.956 AC: 10140 AN: 10602

Middle Eastern (MID) AF: 0.928 AC: 271 AN: 292

European-Non Finnish (NFE) AF: 0.957 AC: 65093 AN: 68018

Other (OTH) AF: 0.920 AC: 1942 AN: 2110

Alfa AF: 0.916 Hom.: 2426

Bravo AF: 0.914

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.37
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs7809799; hg19: chr7-98760504;