rs757647

chr5-138371626-G-Achr5-138371626-G-Cchr5-138371626-G-T

Variant summary

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

The NM_016604.4(KDM3B):c.193-1048G>A 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 151,846 control chromosomes in the GnomAD database, including 7,475 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 (7475 hom., cov: 31)
• Consequence: KDM3B NM_016604.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.755

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM3B	NM_016604.4	c.193-1048G>A		intron_variant		ENST00000314358.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM3B	ENST00000314358.10	c.193-1048G>A		intron_variant		1	NM_016604.4	P1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 44999 AN: 151728 Hom.: 7465 Cov.: 31

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.333

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: 45041 AN: 151846 Hom.: 7475 Cov.: 31 AF XY: 0.302 AC XY: 22412 AN XY: 74210

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.303

Alfa AF: 0.242 Hom.: 8554

Bravo AF: 0.310

Asia WGS AF: 0.446 AC: 1551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	8.7
Dann	Benign	0.43

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: rs757647; hg19: chr5-137707315; COSMIC: COSV58689100; COSMIC: COSV58689100;