dbSNP rs10521482: LOC124900486:n.17836A>T (chrX-56125254-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The XR_007068244.1(LOC124900486):n.17836A>T variant causes a non coding transcript exon 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

LOC124900486
XR_007068244.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.748

Publications

0 publications found

Variant links:

Genes affected

LOC124900486 (HGNC:):

LOC124900486 links:

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]

KLF8 links:

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ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
LOC124900486	XR_007068244.1 link	n.17836A>T	non_coding_transcript_exon_variant	Exon 1 of 2
KLF8	NM_001324104.1 link	c.22+110293A>T	intron_variant	Intron 2 of 6	NP_001311033.1
KLF8	NM_001324105.1 link	c.-2-124977A>T	intron_variant	Intron 1 of 5	NP_001311034.1
LOC124900486	XR_007068245.1 link	n.597+70173A>T	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank
ENSG00000227486	ENST00000655874.2 link	n.449-79719A>T	intron_variant	Intron 2 of 2
ENSG00000227486	ENST00000661602.1 link	n.1010-79719A>T	intron_variant	Intron 4 of 4
ENSG00000227486	ENST00000669152.3 link	n.772-79719A>T	intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.00957

AC:

1069

AN:

111755

Hom.:

Cov.:

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.:

Cov.:

AF XY:

0.00882

AC XY:

300

AN XY:

33996

show subpopulations

African (AFR)

AF:

0.00166

AC:

AN:

30774

American (AMR)

AF:

0.00969

AC:

102

AN:

10530

Ashkenazi Jewish (ASJ)

AF:

0.0155

AC:

AN:

2643

East Asian (EAS)

AF:

0.00

AC:

AN:

3577

South Asian (SAS)

AF:

0.0313

AC:

AN:

2653

European-Finnish (FIN)

AF:

0.00330

AC:

AN:

6069

Middle Eastern (MID)

AF:

0.0183

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.0140

AC:

746

AN:

53134

Other (OTH)

AF:

0.0145

AC:

AN:

1520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

117

156

195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0111

Hom.:

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

(source)

DANN

Benign

0.53

PhyloP100

-0.75

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over