1-202747003-C-T

Variant names:

• chr1-202747003-C-T
• rs2363965
• NM_006618.5:c.2017-680G>A

Variant summary

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

The NM_006618.5(KDM5B):​c.2017-680G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 152,048 control chromosomes in the GnomAD database, including 37,041 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 0.67 (37041 hom., cov: 32)
• Consequence: KDM5B NM_006618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 6 publications found

Genes affected

KDM5B (HGNC:18039): (lysine demethylase 5B) This gene encodes a lysine-specific histone demethylase that belongs to the jumonji/ARID domain-containing family of histone demethylases. The encoded protein is capable of demethylating tri-, di- and monomethylated lysine 4 of histone H3. This protein plays a role in the transcriptional repression or certain tumor suppressor genes and is upregulated in certain cancer cells. This protein may also play a role in genome stability and DNA repair. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

KDM5B Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 65

  Inheritance: AD, AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• intellectual disability

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM5B	NM_006618.5	c.2017-680G>A		intron_variant	Intron 14 of 26	ENST00000367265.9	NP_006609.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM5B	ENST00000367265.9	c.2017-680G>A		intron_variant	Intron 14 of 26	1	NM_006618.5	ENSP00000356234.3

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102257 AN: 151930 Hom.: 37035 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.673 AC: 102299 AN: 152048 Hom.: 37041 Cov.: 32 AF XY: 0.677 AC XY: 50345 AN XY: 74374

African (AFR) AF: 0.378 AC: 15674 AN: 41462

American (AMR) AF: 0.820 AC: 12540 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.825 AC: 2859 AN: 3466

East Asian (EAS) AF: 0.788 AC: 4083 AN: 5180

South Asian (SAS) AF: 0.687 AC: 3315 AN: 4826

European-Finnish (FIN) AF: 0.796 AC: 8419 AN: 10580

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.781 AC: 53052 AN: 67936

Other (OTH) AF: 0.716 AC: 1511 AN: 2110

Alfa AF: 0.753 Hom.: 24675

Bravo AF: 0.662

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.060
DANN	Benign	0.23
PhyloP100		-1.3
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: rs2363965; hg19: chr1-202716131;