9-107487627-TCAGGGCTGCCTTTGCTGACGCTGATGACCGACGGGCTGCCGTACTCGCTGC-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4BP6_ModerateBS2
The NM_004235.6(KLF4):βc.716_766delβ(p.Gly239_Pro255del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00413 in 1,602,948 control chromosomes in the GnomAD database, including 18 homozygotes. Variant has been reported in ClinVar as Likely benign (β ).
Frequency
Genomes: π 0.0033 ( 1 hom., cov: 32)
Exomes π: 0.0042 ( 17 hom. )
Consequence
KLF4
NM_004235.6 inframe_deletion
NM_004235.6 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.79
Genes affected
KLF4 (HGNC:6348): (KLF transcription factor 4) This gene encodes a protein that belongs to the Kruppel family of transcription factors. The encoded zinc finger protein is required for normal development of the barrier function of skin. The encoded protein is thought to control the G1-to-S transition of the cell cycle following DNA damage by mediating the tumor suppressor gene p53. Mice lacking this gene have a normal appearance but lose weight rapidly, and die shortly after birth due to fluid evaporation resulting from compromised epidermal barrier function. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_004235.6.
BP6
Variant 9-107487627-TCAGGGCTGCCTTTGCTGACGCTGATGACCGACGGGCTGCCGTACTCGCTGC-T is Benign according to our data. Variant chr9-107487627-TCAGGGCTGCCTTTGCTGACGCTGATGACCGACGGGCTGCCGTACTCGCTGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 774467.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 507 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KLF4 | NM_004235.6 | c.716_766del | p.Gly239_Pro255del | inframe_deletion | 3/5 | ENST00000374672.5 | NP_004226.3 | |
KLF4 | NM_001314052.2 | c.716_766del | p.Gly239_Pro255del | inframe_deletion | 3/4 | NP_001300981.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KLF4 | ENST00000374672.5 | c.716_766del | p.Gly239_Pro255del | inframe_deletion | 3/5 | 1 | NM_004235.6 | ENSP00000363804 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00334 AC: 508AN: 152096Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00162 AC: 366AN: 226032Hom.: 2 AF XY: 0.00163 AC XY: 204AN XY: 125202
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GnomAD4 exome AF: 0.00422 AC: 6116AN: 1450734Hom.: 17 AF XY: 0.00413 AC XY: 2984AN XY: 721892
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GnomAD4 genome AF: 0.00333 AC: 507AN: 152214Hom.: 1 Cov.: 32 AF XY: 0.00328 AC XY: 244AN XY: 74440
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
KLF4-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 31, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 04, 2018 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at