rs10521482

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001324104.1(KLF8):​c.22+110293A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00956 in 111,804 control chromosomes in the GnomAD database, including 9 homozygotes. There are 300 hemizygotes in GnomAD. 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 0.0096 ( 9 hom., 300 hem., cov: 23)

Consequence

KLF8
NM_001324104.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.748
Variant links:
Genes affected
KLF8 (HGNC:6351): (KLF transcription factor 8) This gene encodes a protein which is a member of the Sp/KLF family of transcription factors. Members of this family contain a C-terminal DNA-binding domain with three Kruppel-like zinc fingers. The encoded protein is thought to play an important role in the regulation of epithelial to mesenchymal transition, a process which occurs normally during development but also during metastasis. A pseudogene has been identified on chromosome 16. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00956 (1069/111804) while in subpopulation SAS AF= 0.0313 (83/2653). AF 95% confidence interval is 0.0259. There are 9 homozygotes in gnomad4. There are 300 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KLF8NM_001324104.1 linkuse as main transcriptc.22+110293A>T intron_variant NP_001311033.1
KLF8NM_001324105.1 linkuse as main transcriptc.-2-124977A>T intron_variant NP_001311034.1
LOC124900486XR_007068244.1 linkuse as main transcriptn.17836A>T non_coding_transcript_exon_variant 1/2
LOC124900486XR_007068245.1 linkuse as main transcriptn.597+70173A>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ENSG00000227486ENST00000655874.1 linkuse as main transcriptn.353-79719A>T intron_variant
ENSG00000227486ENST00000661602.1 linkuse as main transcriptn.1010-79719A>T intron_variant
ENSG00000227486ENST00000669152.2 linkuse as main transcriptn.676-79719A>T intron_variant

Frequencies

GnomAD3 genomes
AF:
0.00957
AC:
1069
AN:
111755
Hom.:
9
Cov.:
23
AF XY:
0.00884
AC XY:
300
AN XY:
33937
show subpopulations
Gnomad AFR
AF:
0.00166
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00970
Gnomad ASJ
AF:
0.0155
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0308
Gnomad FIN
AF:
0.00330
Gnomad MID
AF:
0.0208
Gnomad NFE
AF:
0.0140
Gnomad OTH
AF:
0.0146
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.00956
AC:
1069
AN:
111804
Hom.:
9
Cov.:
23
AF XY:
0.00882
AC XY:
300
AN XY:
33996
show subpopulations
Gnomad4 AFR
AF:
0.00166
Gnomad4 AMR
AF:
0.00969
Gnomad4 ASJ
AF:
0.0155
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0313
Gnomad4 FIN
AF:
0.00330
Gnomad4 NFE
AF:
0.0140
Gnomad4 OTH
AF:
0.0145
Alfa
AF:
0.0111
Hom.:
58
Bravo
AF:
0.00902

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
0.62
DANN
Benign
0.53

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10521482; hg19: chrX-56151687; API