rs17171808

Positions:

• chr5-138363510-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016604.4(KDM3B):​c.193-9164A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,118 control chromosomes in the GnomAD database, including 5,623 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 0.26 (5623 hom., cov: 32)
• Consequence: KDM3B NM_016604.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

Genes affected

KDM3B (HGNC:1337): (lysine demethylase 3B) Predicted to enable chromatin DNA binding activity; histone H3-methyl-lysine-9 demethylase activity; and transcription coregulator activity. Predicted to be involved in histone H3-K9 demethylation and regulation of transcription by RNA polymerase II. Located in nucleoplasm. Biomarker of acute lymphoblastic leukemia; breast cancer; colorectal cancer; and lung non-small cell carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM3B	NM_016604.4	c.193-9164A>G		intron_variant		ENST00000314358.10	NP_057688.3
KDM3B	XM_011543489.3	c.48+8079A>G		intron_variant			XP_011541791.1
KDM3B	XM_047417313.1	c.48+8079A>G		intron_variant			XP_047273269.1
KDM3B	XM_005272018.5	c.193-9164A>G		intron_variant			XP_005272075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM3B	ENST00000314358.10	c.193-9164A>G		intron_variant		1	NM_016604.4	ENSP00000326563.5

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38846 AN: 152002 Hom.: 5616 Cov.: 32

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.256 AC: 38872 AN: 152118 Hom.: 5623 Cov.: 32 AF XY: 0.260 AC XY: 19302 AN XY: 74380

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.562

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.269

Alfa AF: 0.235 Hom.: 965

Bravo AF: 0.270

Asia WGS AF: 0.352 AC: 1223 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.1
DANN	Benign	0.37

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

LitVar

Other links and lift over

dbSNP: rs17171808; hg19: chr5-137699199; COSMIC: COSV58689048;