rs387906223

Positions:

• chr3-49171662-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP5 BP4 BS2_Supporting

The NM_173546.3(KLHDC8B):​c.-158C>T variant causes a 5 prime UTR 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 Pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.0047 (2 hom., cov: 33)
  • Exomes 𝑓: 0.021 (0 hom.)
• Consequence: KLHDC8B NM_173546.3 5_prime_UTR
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.456

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]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PP5: Variant 3-49171662-C-T is Pathogenic according to our data. Variant chr3-49171662-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 273.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79). . Strength limited to SUPPORTING due to the PP5.
• 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/exons	MANE	Protein	UniProt
KLHDC8B	NM_173546.3	c.-158C>T		5_prime_UTR_variant	1/6	ENST00000332780.4	NP_775817.1
KLHDC8B	XM_005264938.4	c.-158C>T		5_prime_UTR_variant	1/6		XP_005264995.1
KLHDC8B	XM_006713015.4	c.-158C>T		5_prime_UTR_variant	1/6		XP_006713078.1
KLHDC8B	XM_006713016.4	c.-158C>T		5_prime_UTR_variant	1/6		XP_006713079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHDC8B	ENST00000332780.4	c.-158C>T		5_prime_UTR_variant	1/6	1	NM_173546.3	ENSP00000327468	P1
KLHDC8B	ENST00000459846.6	n.41C>T		non_coding_transcript_exon_variant	1/5	3

Frequencies

GnomAD3 genomes AF: 0.00472 AC: 718 AN: 152248 Hom.: 2 Cov.: 33

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

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

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: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Classic Hodgkin lymphoma Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 01, 2009

- -

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

Other links and lift over

dbSNP: rs387906223; hg19: chr3-49209095;