dbSNP rs2032673: KDM5D:c.1093-7A>G (chrY-19732172-T-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_004653.5(KDM5D):c.1093-7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0067 ( 0 hom., 217 hem., cov: 0)

Exomes 𝑓: 0.013 ( 0 hom. 4698 hem. )

Consequence

KDM5D
NM_004653.5 splice_region, intron

Scores

Splicing: ADA: 0.00004107

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.49

Publications

14 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

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=-0.89).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM5D	NM_004653.5 link	c.1093-7A>G		splice_region_variant, intron_variant	Intron 9 of 26	ENST00000317961.9	NP_004644.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM5D	ENST00000317961.9 link	c.1093-7A>G		splice_region_variant, intron_variant	Intron 9 of 26	1	NM_004653.5	ENSP00000322408.4

Frequencies

GnomAD3 genomes

AF:

0.00660

AC:

214

AN:

32409

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000281

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.149

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000301

Gnomad OTH

AF:

0.00226

GnomAD2 exomes

AF:

0.0265

AC:

1512

AN:

57102

AF XY:

0.0265

show subpopulations

Gnomad AFR exome

AF:

0.00118

Gnomad AMR exome

AF:

0.000624

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000251

Gnomad FIN exome

AF:

0.000197

Gnomad NFE exome

AF:

0.00108

Gnomad OTH exome

AF:

0.0129

GnomAD4 exome

AF:

0.0132

AC:

4698

AN:

355816

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

4698

AN XY:

355816

show subpopulations

African (AFR)

AF:

0.000719

AC:

AN:

6958

American (AMR)

AF:

0.000547

AC:

AN:

9134

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6650

East Asian (EAS)

AF:

0.000107

AC:

AN:

9374

South Asian (SAS)

AF:

0.137

AC:

4296

AN:

31321

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12551

Middle Eastern (MID)

AF:

0.00434

AC:

AN:

1613

European-Non Finnish (NFE)

AF:

0.000731

AC:

193

AN:

264177

Other (OTH)

AF:

0.0136

AC:

191

AN:

14038

Age Distribution

Exome Hom

Variant carriers

108

162

216

270

<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:

0.00668

AC:

217

AN:

32473

Hom.:

Cov.:

AF XY:

0.00668

AC XY:

217

AN XY:

32473

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

8283

American (AMR)

AF:

0.000280

AC:

AN:

3571

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

755

East Asian (EAS)

AF:

0.00

AC:

AN:

1212

South Asian (SAS)

AF:

0.151

AC:

209

AN:

1384

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3264

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000301

AC:

AN:

13273

Other (OTH)

AF:

0.00224

AC:

AN:

446

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:

0.0900

Hom.:

4305

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.9

(source)

DANN

Benign

0.38

PhyloP100

-2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000041

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.020

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