dbSNP rs16976587: KDM8:c.-32+27G>A (chr16-27203663-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_024773.3(KDM8):c.-32+27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 164,834 control chromosomes in the GnomAD database, including 137 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 0.024 ( 136 hom., cov: 34)

Exomes 𝑓: 0.0036 ( 1 hom. )

Consequence

KDM8
NM_024773.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.188

Publications

7 publications found

Variant links:

Genes affected

KDM8 (HGNC:25840): (lysine demethylase 8) This gene likely encodes a histone lysine demethylase. Studies of a similar protein in mouse indicate a potential role for this protein as a tumor suppressor. Alternatively spliced transcript variants have been described.[provided by RefSeq, Feb 2009]

KDM8 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=-0.74).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.078 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
KDM8	NM_024773.3 link	c.-32+27G>A	intron_variant	Intron 1 of 7	ENST00000286096.9	NP_079049.2
KDM8	XM_017023676.2 link	c.-32+27G>A	intron_variant	Intron 1 of 6		XP_016879165.1
KDM8	XM_047434654.1 link	c.-32+27G>A	intron_variant	Intron 1 of 4		XP_047290610.1
KDM8	XM_047434655.1 link	c.-32+27G>A	intron_variant	Intron 1 of 6		XP_047290611.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
KDM8	ENST00000286096.9 link	c.-32+27G>A	intron_variant	Intron 1 of 7	1	NM_024773.3	ENSP00000286096.5
KDM8	ENST00000564961.1 link	n.129+27G>A	intron_variant	Intron 1 of 4	1
KDM8	ENST00000562269.1 link	n.120+27G>A	intron_variant	Intron 1 of 3	3
KDM8	ENST00000569329.1 link	c.-234G>A	upstream_gene_variant		2		ENSP00000456107.1

Frequencies

GnomAD3 genomes

AF:

0.0236

AC:

3600

AN:

152236

Hom.:

134

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0800

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.0182

GnomAD4 exome

AF:

0.00361

AC:

AN:

12480

Hom.:

Cov.:

AF XY:

0.00232

AC XY:

AN XY:

6890

show subpopulations

African (AFR)

AF:

0.0674

AC:

AN:

386

American (AMR)

AF:

0.00937

AC:

AN:

640

Ashkenazi Jewish (ASJ)

AF:

0.00209

AC:

AN:

478

East Asian (EAS)

AF:

0.00

AC:

AN:

554

South Asian (SAS)

AF:

0.00

AC:

AN:

1904

European-Finnish (FIN)

AF:

0.00

AC:

AN:

506

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000548

AC:

AN:

7294

Other (OTH)

AF:

0.0117

AC:

AN:

682

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0238

AC:

3620

AN:

152354

Hom.:

136

Cov.:

AF XY:

0.0229

AC XY:

1704

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.0803

AC:

3337

AN:

41568

American (AMR)

AF:

0.0114

AC:

175

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00230

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000828

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000720

AC:

AN:

68034

Other (OTH)

AF:

0.0180

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

173

347

520

694

867

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0250

Hom.:

Bravo

AF:

0.0263

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.2

(source)

DANN

Benign

0.87

PhyloP100

-0.19

PromoterAI

0.017

Neutral

(source)

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