rs387906223

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBS2_Supporting

The NM_173546.3(KLHDC8B):​c.-158C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00473 in 152,510 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 2 hom., cov: 33)
Exomes 𝑓: 0.021 ( 0 hom. )

Consequence

KLHDC8B
NM_173546.3 5_prime_UTR_premature_start_codon_gain

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter P:1B:1

Conservation

PhyloP100: 0.456
Variant links:
Genes affected
KLHDC8B (HGNC:28557): (kelch domain containing 8B) This gene encodes a protein which forms a distinct beta-propeller protein structure of kelch domains allowing for protein-protein interactions. Mutations in this gene have been associated with Hodgkin lymphoma. [provided by RefSeq, Sep 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 3-49171662-C-T is Benign according to our data. Variant chr3-49171662-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 273.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 718 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KLHDC8BNM_173546.3 linkc.-158C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 6 ENST00000332780.4 NP_775817.1 Q8IXV7Q96DZ8
KLHDC8BNM_173546.3 linkc.-158C>T 5_prime_UTR_variant Exon 1 of 6 ENST00000332780.4 NP_775817.1 Q8IXV7Q96DZ8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KLHDC8BENST00000332780 linkc.-158C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 6 1 NM_173546.3 ENSP00000327468.2 Q8IXV7
KLHDC8BENST00000332780 linkc.-158C>T 5_prime_UTR_variant Exon 1 of 6 1 NM_173546.3 ENSP00000327468.2 Q8IXV7
KLHDC8BENST00000459846.6 linkn.41C>T non_coding_transcript_exon_variant Exon 1 of 5 3

Frequencies

GnomAD3 genomes
AF:
0.00472
AC:
718
AN:
152248
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00157
Gnomad AMI
AF:
0.00987
Gnomad AMR
AF:
0.00229
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00103
Gnomad FIN
AF:
0.00461
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00807
Gnomad OTH
AF:
0.00287
GnomAD4 exome
AF:
0.0208
AC:
3
AN:
144
Hom.:
0
Cov.:
0
AF XY:
0.0273
AC XY:
3
AN XY:
110
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0242
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00471
AC:
718
AN:
152366
Hom.:
2
Cov.:
33
AF XY:
0.00431
AC XY:
321
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.00156
Gnomad4 AMR
AF:
0.00229
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00103
Gnomad4 FIN
AF:
0.00461
Gnomad4 NFE
AF:
0.00807
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00507
Hom.:
0
Bravo
AF:
0.00446
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Pathogenic:1Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Classic Hodgkin lymphoma Pathogenic:1
Sep 01, 2009
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only

- -

not provided Benign:1
Feb 01, 2025
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

KLHDC8B: BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
8.9
DANN
Benign
0.69

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: rs387906223; hg19: chr3-49209095; API