rs17171808

Variant names:

• chr5-138363510-A-G
• rs17171808
• NM_016604.4:c.193-9164A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

KDM3B Gene-Disease associations (from GenCC):

• Diets-Jongmans syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KDM3B	NM_016604.4	c.193-9164A>G		intron_variant	Intron 1 of 23	ENST00000314358.10	NP_057688.3
KDM3B	XM_011543489.3	c.48+8079A>G		intron_variant	Intron 1 of 23		XP_011541791.1
KDM3B	XM_047417313.1	c.48+8079A>G		intron_variant	Intron 2 of 24		XP_047273269.1
KDM3B	XM_005272018.5	c.193-9164A>G		intron_variant	Intron 1 of 22		XP_005272075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM3B	ENST00000314358.10	c.193-9164A>G		intron_variant	Intron 1 of 23	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

African (AFR) AF: 0.350 AC: 14540 AN: 41486

American (AMR) AF: 0.261 AC: 3994 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 988 AN: 3470

East Asian (EAS) AF: 0.562 AC: 2904 AN: 5168

South Asian (SAS) AF: 0.183 AC: 884 AN: 4824

European-Finnish (FIN) AF: 0.205 AC: 2170 AN: 10578

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12441 AN: 67980

Other (OTH) AF: 0.269 AC: 568 AN: 2112

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
PhyloP100		-0.092
Mutation Taster		=100/0	polymorphism (auto)

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