rs2032640

Variant names:

• chrY-19730686-C-T
• rs2032640
• NM_004653.5:c.1371+1086G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004653.5(KDM5D):​c.1371+1086G>A 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 0.0065 (0 hom., 197 hem., cov: 0)
• Consequence: KDM5D NM_004653.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• Publications: 10 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00654 (197/30137) while in subpopulation AMR AF = 0.034 (122/3593). AF 95% confidence interval is 0.0291. There are 0 homozygotes in GnomAd4. There are 197 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 197 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM5D	NM_004653.5	MANE Select	c.1371+1086G>A		intron	N/A	NP_004644.2
	KDM5D	NM_001146705.2		c.1371+1086G>A		intron	N/A	NP_001140177.1
	KDM5D	NM_001146706.2		c.1200+1086G>A		intron	N/A	NP_001140178.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM5D	ENST00000317961.9	TSL:1 MANE Select	c.1371+1086G>A		intron	N/A	ENSP00000322408.4
	KDM5D	ENST00000541639.5	TSL:1	c.1371+1086G>A		intron	N/A	ENSP00000444293.1
	KDM5D	ENST00000382806.6	TSL:1	c.1200+1086G>A		intron	N/A	ENSP00000372256.2

Frequencies

GnomAD3 genomes AF: 0.00652 AC: 196 AN: 30075 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00201

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0340

Gnomad ASJ AF: 0.0132

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.211

Gnomad NFE AF: 0.00178

Gnomad OTH AF: 0.0176

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00654 AC: 197 AN: 30137 Hom.: 0 Cov.: 0 AF XY: 0.00654 AC XY: 197 AN XY: 30137

African (AFR) AF: 0.00200 AC: 17 AN: 8518

American (AMR) AF: 0.0340 AC: 122 AN: 3593

Ashkenazi Jewish (ASJ) AF: 0.0132 AC: 10 AN: 760

East Asian (EAS) AF: 0.000772 AC: 1 AN: 1295

South Asian (SAS) AF: 0.00 AC: 0 AN: 1474

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 800

Middle Eastern (MID) AF: 0.222 AC: 16 AN: 72

European-Non Finnish (NFE) AF: 0.00178 AC: 23 AN: 12952

Other (OTH) AF: 0.0175 AC: 8 AN: 458

Alfa AF: 0.0398 Hom.: 1121

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.9
DANN	Benign	0.56
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs2032640; hg19: chrY-21892572;