dbSNP rs2032672: KDM5D:c.1212+51T>G (chrY-19731995-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_004653.5(KDM5D):c.1212+51T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0063 ( 0 hom., 210 hem., cov: 0)

Exomes 𝑓: 0.0058 ( 0 hom. 2076 hem. )

Consequence

KDM5D
NM_004653.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.191

Publications

8 publications found

Variant links:

Genes affected

KDM5D (HGNC:11115): (lysine demethylase 5D) This gene encodes a protein containing zinc finger domains. A short peptide derived from this protein is a minor histocompatibility antigen which can lead to graft rejection of male donor cells in a female recipient. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

KDM5D links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_004653.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.93).

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00577 (2076/359697) while in subpopulation MID AF = 0.0523 (85/1624). AF 95% confidence interval is 0.0434. There are 0 homozygotes in GnomAdExome4. There are 2076 alleles in the male GnomAdExome4 subpopulation. Median coverage is 8. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 210 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004653.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KDM5D	NM_004653.5	MANE Select	c.1212+51T>G	intron	N/A	NP_004644.2
KDM5D	NM_001146705.2		c.1212+51T>G	intron	N/A	NP_001140177.1	Q9BY66-3
KDM5D	NM_001146706.2		c.1041+51T>G	intron	N/A	NP_001140178.1	Q9BY66-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KDM5D	ENST00000317961.9	TSL:1 MANE Select	c.1212+51T>G	intron	N/A	ENSP00000322408.4	Q9BY66-1
KDM5D	ENST00000541639.5	TSL:1	c.1212+51T>G	intron	N/A	ENSP00000444293.1	Q9BY66-3
KDM5D	ENST00000382806.6	TSL:1	c.1041+51T>G	intron	N/A	ENSP00000372256.2	Q9BY66-2

Frequencies

GnomAD3 genomes

AF:

0.00633

AC:

210

AN:

33189

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00202

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0156

Gnomad ASJ

AF:

0.0452

Gnomad EAS

AF:

0.000801

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00681

Gnomad OTH

AF:

0.0132

GnomAD2 exomes

AF:

0.00828

AC:

561

AN:

67713

AF XY:

0.00828

show subpopulations

Gnomad AFR exome

AF:

0.000324

Gnomad AMR exome

AF:

0.0146

Gnomad ASJ exome

AF:

0.0341

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000178

Gnomad NFE exome

AF:

0.00838

Gnomad OTH exome

AF:

0.0157

GnomAD4 exome

AF:

0.00577

AC:

2076

AN:

359697

Hom.:

Cov.:

AF XY:

0.00577

AC XY:

2076

AN XY:

359697

show subpopulations

African (AFR)

AF:

0.00484

AC:

AN:

7032

American (AMR)

AF:

0.0165

AC:

157

AN:

9510

Ashkenazi Jewish (ASJ)

AF:

0.0301

AC:

202

AN:

6722

East Asian (EAS)

AF:

0.00

AC:

AN:

9474

South Asian (SAS)

AF:

0.00799

AC:

256

AN:

32025

European-Finnish (FIN)

AF:

0.0000777

AC:

AN:

12870

Middle Eastern (MID)

AF:

0.0523

AC:

AN:

1624

European-Non Finnish (NFE)

AF:

0.00445

AC:

1186

AN:

266257

Other (OTH)

AF:

0.0109

AC:

155

AN:

14183

Age Distribution

Exome Hom

Variant carriers

114

152

190

<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:

0.00632

AC:

210

AN:

33254

Hom.:

Cov.:

AF XY:

0.00632

AC XY:

210

AN XY:

33254

show subpopulations

African (AFR)

AF:

0.00201

AC:

AN:

8477

American (AMR)

AF:

0.0155

AC:

AN:

3666

Ashkenazi Jewish (ASJ)

AF:

0.0452

AC:

AN:

752

East Asian (EAS)

AF:

0.000801

AC:

AN:

1248

South Asian (SAS)

AF:

0.00206

AC:

AN:

1453

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3407

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00681

AC:

AN:

13506

Other (OTH)

AF:

0.0132

AC:

AN:

456

Age Distribution

Genome Hom

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:

0.0262

Hom.:

460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.5

(source)

DANN

Benign

0.25

PhyloP100

0.19

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over