dbSNP rs387906223: KLHDC8B:c.-158C>T (chr3-49171662-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -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

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]

KLHDC8B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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
KLHDC8B	NM_173546.3 link	c.-158C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	ENST00000332780.4	NP_775817.1	Q8IXV7Q96DZ8
KLHDC8B	NM_173546.3 link	c.-158C>T		5_prime_UTR_variant	Exon 1 of 6	ENST00000332780.4	NP_775817.1	Q8IXV7Q96DZ8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KLHDC8B	ENST00000332780 link	c.-158C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	1	NM_173546.3	ENSP00000327468.2	Q8IXV7
KLHDC8B	ENST00000332780 link	c.-158C>T	5_prime_UTR_variant	Exon 1 of 6	1	NM_173546.3	ENSP00000327468.2	Q8IXV7
KLHDC8B	ENST00000459846.6 link	n.41C>T	non_coding_transcript_exon_variant	Exon 1 of 5	3

Frequencies

GnomAD3 genomes

AF:

0.00472

AC:

718

AN:

152248

Hom.:

Cov.:

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:

AN:

144

Hom.:

Cov.:

AF XY:

0.0273

AC XY:

AN XY:

110

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

Gnomad4 ASJ exome

AC:

AN:

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

Gnomad4 NFE exome

AF:

0.0242

AC:

AN:

124

Gnomad4 Remaining exome

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00471

AC:

718

AN:

152366

Hom.:

Cov.:

AF XY:

0.00431

AC XY:

321

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00156

AC:

0.00156258

AN:

0.00156258

Gnomad4 AMR

AF:

0.00229

AC:

0.00228668

AN:

0.00228668

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00103

AC:

0.00103434

AN:

0.00103434

Gnomad4 FIN

AF:

0.00461

AC:

0.00461046

AN:

0.00461046

Gnomad4 NFE

AF:

0.00807

AC:

0.00806973

AN:

0.00806973

Gnomad4 OTH

AF:

0.00284

AC:

0.00283822

AN:

0.00283822

Heterozygous variant carriers

110

147

184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<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:

0.00351

Hom.:

Bravo

AF:

0.00446

Asia WGS

AF:

0.000289

AC:

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

Mutation Taster

=300/0

disease causing (ClinVar)

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over