rs1540209

Variant names:

• chr11-68161053-A-C
• rs1540209
• NM_017635.5:c.1175-1882T>G

Your query was ambiguous. Multiple possible variants found:

• chr11-68161053-A-C
• chr11-68161053-A-G
• chr11-68161053-A-T

Variant summary

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

The NM_017635.5(KMT5B):​c.1175-1882T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 152,038 control chromosomes in the GnomAD database, including 34,077 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 0.66 (34077 hom., cov: 32)
• Consequence: KMT5B NM_017635.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389
• Publications: 7 publications found

Genes affected

KMT5B (HGNC:24283): (lysine methyltransferase 5B) This gene encodes a protein that contains a SET domain. SET domains appear to be protein-protein interaction domains that mediate interactions with a family of proteins that display similarity with dual-specificity phosphatases (dsPTPases). The function of this gene has not been determined. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

KMT5B Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• intellectual disability, autosomal dominant 51

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT5B	NM_017635.5	c.1175-1882T>G		intron_variant	Intron 10 of 10	ENST00000304363.9	NP_060105.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KMT5B	ENST00000304363.9	c.1175-1882T>G		intron_variant	Intron 10 of 10	5	NM_017635.5	ENSP00000305899.4

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100828 AN: 151920 Hom.: 34026 Cov.: 32

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.732

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.664 AC: 100935 AN: 152038 Hom.: 34077 Cov.: 32 AF XY: 0.669 AC XY: 49731 AN XY: 74304

African (AFR) AF: 0.733 AC: 30398 AN: 41462

American (AMR) AF: 0.713 AC: 10889 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2062 AN: 3468

East Asian (EAS) AF: 0.890 AC: 4607 AN: 5178

South Asian (SAS) AF: 0.781 AC: 3763 AN: 4816

European-Finnish (FIN) AF: 0.598 AC: 6316 AN: 10562

Middle Eastern (MID) AF: 0.736 AC: 215 AN: 292

European-Non Finnish (NFE) AF: 0.597 AC: 40600 AN: 67968

Other (OTH) AF: 0.670 AC: 1414 AN: 2112

Alfa AF: 0.626 Hom.: 34896

Bravo AF: 0.680

Asia WGS AF: 0.822 AC: 2858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.3
DANN	Benign	0.44
PhyloP100		-0.39
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: rs1540209; hg19: chr11-67928520;