3-183650217-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017644.3(KLHL24):​c.-61-79G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 636,122 control chromosomes in the GnomAD database, including 27,578 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8193 hom., cov: 32)
Exomes 𝑓: 0.27 ( 19385 hom. )

Consequence

KLHL24
NM_017644.3 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.504
Variant links:
Genes affected
KLHL24 (HGNC:25947): (kelch like family member 24) The protein encoded by this gene is a ubiquitin ligase substrate receptor and is regulated by autoubiquitination. Variations in the translation initiation codon of this gene have been found, which result in an N-terminally truncated but more stable protein due to loss of the autoubiquitination function. The more stable mutant protein causes an increased ubiquitin and degradation of keratin 14, which leads to skin fragility and the potentially life-threatening disease epidermolysis bullosa. The encoded protein is also involved in the regulation of kainate receptors. [provided by RefSeq, Mar 2017]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 3-183650217-G-A is Benign according to our data. Variant chr3-183650217-G-A is described in ClinVar as [Benign]. Clinvar id is 1288159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KLHL24NM_017644.3 linkuse as main transcriptc.-61-79G>A intron_variant ENST00000242810.11 NP_060114.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KLHL24ENST00000242810.11 linkuse as main transcriptc.-61-79G>A intron_variant 1 NM_017644.3 ENSP00000242810.6 Q6TFL4-1

Frequencies

GnomAD3 genomes
AF:
0.318
AC:
48262
AN:
151884
Hom.:
8183
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.428
Gnomad AMI
AF:
0.368
Gnomad AMR
AF:
0.313
Gnomad ASJ
AF:
0.280
Gnomad EAS
AF:
0.476
Gnomad SAS
AF:
0.189
Gnomad FIN
AF:
0.229
Gnomad MID
AF:
0.383
Gnomad NFE
AF:
0.263
Gnomad OTH
AF:
0.333
GnomAD4 exome
AF:
0.274
AC:
132614
AN:
484120
Hom.:
19385
AF XY:
0.269
AC XY:
68093
AN XY:
253044
show subpopulations
Gnomad4 AFR exome
AF:
0.437
Gnomad4 AMR exome
AF:
0.293
Gnomad4 ASJ exome
AF:
0.278
Gnomad4 EAS exome
AF:
0.468
Gnomad4 SAS exome
AF:
0.192
Gnomad4 FIN exome
AF:
0.223
Gnomad4 NFE exome
AF:
0.262
Gnomad4 OTH exome
AF:
0.286
GnomAD4 genome
AF:
0.318
AC:
48313
AN:
152002
Hom.:
8193
Cov.:
32
AF XY:
0.313
AC XY:
23243
AN XY:
74296
show subpopulations
Gnomad4 AFR
AF:
0.428
Gnomad4 AMR
AF:
0.313
Gnomad4 ASJ
AF:
0.280
Gnomad4 EAS
AF:
0.476
Gnomad4 SAS
AF:
0.188
Gnomad4 FIN
AF:
0.229
Gnomad4 NFE
AF:
0.263
Gnomad4 OTH
AF:
0.336
Alfa
AF:
0.282
Hom.:
792
Bravo
AF:
0.336
Asia WGS
AF:
0.320
AC:
1112
AN:
3476

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxMay 12, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
1.9
DANN
Benign
0.56
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: rs3755649; hg19: chr3-183368005; API