5-138389314-C-T

Variant names:

• chr5-138389314-C-T
• rs17171818
• NM_016604.4:c.1381-1699C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016604.4(KDM3B):​c.1381-1699C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,044 control chromosomes in the GnomAD database, including 7,540 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 0.30 (7540 hom., cov: 33)
• Consequence: KDM3B NM_016604.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.609
• Publications: 16 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016604.4. 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
	KDM3B	NM_016604.4	MANE Select	c.1381-1699C>T		intron	N/A	NP_057688.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM3B	ENST00000314358.10	TSL:1 MANE Select	c.1381-1699C>T		intron	N/A	ENSP00000326563.5
	KDM3B	ENST00000510866.5	TSL:1	n.*266-1699C>T		intron	N/A	ENSP00000425186.1
	KDM3B	ENST00000507996.5	TSL:2	n.45+2693C>T		intron	N/A	ENSP00000423012.1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45154 AN: 151926 Hom.: 7530 Cov.: 33

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.297 AC: 45195 AN: 152044 Hom.: 7540 Cov.: 33 AF XY: 0.303 AC XY: 22489 AN XY: 74310

African (AFR) AF: 0.411 AC: 17024 AN: 41440

American (AMR) AF: 0.290 AC: 4427 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1106 AN: 3470

East Asian (EAS) AF: 0.573 AC: 2969 AN: 5178

South Asian (SAS) AF: 0.294 AC: 1417 AN: 4818

European-Finnish (FIN) AF: 0.235 AC: 2485 AN: 10572

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14617 AN: 67960

Other (OTH) AF: 0.304 AC: 643 AN: 2116

Alfa AF: 0.243 Hom.: 8389

Bravo AF: 0.310

Asia WGS AF: 0.446 AC: 1553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.51
DANN	Benign	0.62
PhyloP100		-0.61
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: rs17171818; hg19: chr5-137725003; COSMIC: COSV58689175;