rs7617480

Positions:

• chr3-49173299-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173546.3(KLHDC8B):​c.376+154A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 787,430 control chromosomes in the GnomAD database, including 249,018 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.77 (45169 hom., cov: 33)
  • Exomes 𝑓: 0.80 (203849 hom.)
• Consequence: KLHDC8B NM_173546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHDC8B	NM_173546.3	c.376+154A>C		intron_variant		ENST00000332780.4	NP_775817.1
KLHDC8B	XM_005264938.4	c.376+154A>C		intron_variant			XP_005264995.1
KLHDC8B	XM_006713015.4	c.406+124A>C		intron_variant			XP_006713078.1
KLHDC8B	XM_006713016.4	c.406+124A>C		intron_variant			XP_006713079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHDC8B	ENST00000332780.4	c.376+154A>C		intron_variant		1	NM_173546.3	ENSP00000327468	P1
KLHDC8B	ENST00000459846.6	n.230+498A>C		intron_variant, non_coding_transcript_variant		3
KLHDC8B	ENST00000476495.2	n.463+124A>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116526 AN: 152066 Hom.: 45147 Cov.: 33

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.752

GnomAD4 exome AF: 0.798 AC: 506740 AN: 635246 Hom.: 203849 AF XY: 0.802 AC XY: 259662 AN XY: 323606

Gnomad4 AFR exome AF: 0.671

Gnomad4 AMR exome AF: 0.853

Gnomad4 ASJ exome AF: 0.804

Gnomad4 EAS exome AF: 0.998

Gnomad4 SAS exome AF: 0.920

Gnomad4 FIN exome AF: 0.844

Gnomad4 NFE exome AF: 0.770

Gnomad4 OTH exome AF: 0.791

GnomAD4 genome AF: 0.766 AC: 116596 AN: 152184 Hom.: 45169 Cov.: 33 AF XY: 0.775 AC XY: 57647 AN XY: 74406

Gnomad4 AFR AF: 0.674

Gnomad4 AMR AF: 0.818

Gnomad4 ASJ AF: 0.808

Gnomad4 EAS AF: 0.992

Gnomad4 SAS AF: 0.918

Gnomad4 FIN AF: 0.863

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.755

Alfa AF: 0.774 Hom.: 100215

Bravo AF: 0.758

Asia WGS AF: 0.936 AC: 3254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.7
DANN	Benign	0.75

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: rs7617480; hg19: chr3-49210732;