dbSNP rs7617480: KLHDC8B:c.376+154A>C (chr3-49173299-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.269

Publications

66 publications found

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 Gene-Disease associations (from GenCC):

classic Hodgkin lymphoma
Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

KLHDC8B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
KLHDC8B	NM_173546.3 link	c.376+154A>C	intron_variant	Intron 2 of 5	ENST00000332780.4	NP_775817.1	Q8IXV7Q96DZ8
KLHDC8B	XM_006713015.4 link	c.406+124A>C	intron_variant	Intron 2 of 5		XP_006713078.1
KLHDC8B	XM_006713016.4 link	c.406+124A>C	intron_variant	Intron 2 of 5		XP_006713079.1
KLHDC8B	XM_005264938.4 link	c.376+154A>C	intron_variant	Intron 2 of 5		XP_005264995.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KLHDC8B	ENST00000332780.4 link	c.376+154A>C	intron_variant	Intron 2 of 5	1	NM_173546.3	ENSP00000327468.2	Q8IXV7
KLHDC8B	ENST00000459846.6 link	n.230+498A>C	intron_variant	Intron 2 of 4	3
KLHDC8B	ENST00000476495.2 link	n.463+124A>C	intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.766

AC:

116526

AN:

152066

Hom.:

45147

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.671

AC:

10772

AN:

16044

American (AMR)

AF:

0.853

AC:

16146

AN:

18924

Ashkenazi Jewish (ASJ)

AF:

0.804

AC:

11832

AN:

14708

East Asian (EAS)

AF:

0.998

AC:

31844

AN:

31904

South Asian (SAS)

AF:

0.920

AC:

43651

AN:

47462

European-Finnish (FIN)

AF:

0.844

AC:

24955

AN:

29554

Middle Eastern (MID)

AF:

0.702

AC:

1637

AN:

2332

European-Non Finnish (NFE)

AF:

0.770

AC:

340489

AN:

442188

Other (OTH)

AF:

0.791

AC:

25414

AN:

32130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

5077

10153

15230

20306

25383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5306

10612

15918

21224

26530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.766

AC:

116596

AN:

152184

Hom.:

45169

Cov.:

AF XY:

0.775

AC XY:

57647

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.674

AC:

27989

AN:

41514

American (AMR)

AF:

0.818

AC:

12511

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.808

AC:

2805

AN:

3472

East Asian (EAS)

AF:

0.992

AC:

5144

AN:

5186

South Asian (SAS)

AF:

0.918

AC:

4428

AN:

4826

European-Finnish (FIN)

AF:

0.863

AC:

9148

AN:

10604

Middle Eastern (MID)

AF:

0.711

AC:

209

AN:

294

European-Non Finnish (NFE)

AF:

0.766

AC:

52056

AN:

67980

Other (OTH)

AF:

0.755

AC:

1591

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1416

2831

4247

5662

7078

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

856

1712

2568

3424

4280

<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:

0.772

Hom.:

188767

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

(source)

DANN

Benign

0.75

PhyloP100

0.27

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over