rs10521482

Variant names:

• chrX-56125254-A-T
• rs10521482
• NM_001324104.1:c.22+110293A>T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.748
• Publications: 0 publications found

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]

LOC124900486 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001324104.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF8	NM_001324104.1		c.22+110293A>T		intron	N/A	NP_001311033.1
	KLF8	NM_001324105.1		c.-2-124977A>T		intron	N/A	NP_001311034.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000227486	ENST00000655874.2		n.449-79719A>T		intron	N/A
	ENSG00000227486	ENST00000661602.1		n.1010-79719A>T		intron	N/A
	ENSG00000227486	ENST00000669152.3		n.772-79719A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00957 AC: 1069 AN: 111755 Hom.: 9 Cov.: 23

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

African (AFR) AF: 0.00166 AC: 51 AN: 30774

American (AMR) AF: 0.00969 AC: 102 AN: 10530

Ashkenazi Jewish (ASJ) AF: 0.0155 AC: 41 AN: 2643

East Asian (EAS) AF: 0.00 AC: 0 AN: 3577

South Asian (SAS) AF: 0.0313 AC: 83 AN: 2653

European-Finnish (FIN) AF: 0.00330 AC: 20 AN: 6069

Middle Eastern (MID) AF: 0.0183 AC: 4 AN: 219

European-Non Finnish (NFE) AF: 0.0140 AC: 746 AN: 53134

Other (OTH) AF: 0.0145 AC: 22 AN: 1520

Alfa AF: 0.0111 Hom.: 58

Bravo AF: 0.00902

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.62
DANN	Benign	0.53
PhyloP100		-0.75

Splicing

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

Other links and lift over

dbSNP: rs10521482; hg19: chrX-56151687;