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):​c.716_766del​(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: 𝑓 0.0033 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0042 ( 17 hom. )

Consequence

KLF4
NM_004235.6 inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.79
Variant links:
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
KLF4NM_004235.6 linkuse as main transcriptc.716_766del p.Gly239_Pro255del inframe_deletion 3/5 ENST00000374672.5 NP_004226.3
KLF4NM_001314052.2 linkuse as main transcriptc.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
KLF4ENST00000374672.5 linkuse as main transcriptc.716_766del p.Gly239_Pro255del inframe_deletion 3/51 NM_004235.6 ENSP00000363804 P1O43474-1

Frequencies

GnomAD3 genomes
AF:
0.00334
AC:
508
AN:
152096
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00118
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00976
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.0222
Gnomad NFE
AF:
0.00421
Gnomad OTH
AF:
0.00766
GnomAD3 exomes
AF:
0.00162
AC:
366
AN:
226032
Hom.:
2
AF XY:
0.00163
AC XY:
204
AN XY:
125202
show subpopulations
Gnomad AFR exome
AF:
0.000573
Gnomad AMR exome
AF:
0.00269
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000677
Gnomad NFE exome
AF:
0.00249
Gnomad OTH exome
AF:
0.00267
GnomAD4 exome
AF:
0.00422
AC:
6116
AN:
1450734
Hom.:
17
AF XY:
0.00413
AC XY:
2984
AN XY:
721892
show subpopulations
Gnomad4 AFR exome
AF:
0.000479
Gnomad4 AMR exome
AF:
0.00383
Gnomad4 ASJ exome
AF:
0.0000384
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.000134
Gnomad4 NFE exome
AF:
0.00507
Gnomad4 OTH exome
AF:
0.00464
GnomAD4 genome
AF:
0.00333
AC:
507
AN:
152214
Hom.:
1
Cov.:
32
AF XY:
0.00328
AC XY:
244
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.00116
Gnomad4 AMR
AF:
0.00975
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.00421
Gnomad4 OTH
AF:
0.00758
Alfa
AF:
0.00197
Hom.:
0
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 providedclinical testingPreventionGenetics, part of Exact SciencesJul 31, 2020This 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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpSep 04, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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: rs869299423; hg19: chr9-110249908; API