NM_032482.3:c.201-796A>G

Variant names:

• chr19-2188936-A-G
• rs8113528
• NM_032482.3:c.201-796A>G

Variant summary

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

The NM_032482.3(DOT1L):​c.201-796A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 152,184 control chromosomes in the GnomAD database, including 54,945 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 0.84 (54945 hom., cov: 33)
• Consequence: DOT1L NM_032482.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.10
• Publications: 4 publications found

Genes affected

DOT1L (HGNC:24948): (DOT1 like histone lysine methyltransferase) The protein encoded by this gene is a histone methyltransferase that methylates lysine-79 of histone H3. It is inactive against free core histones, but shows significant histone methyltransferase activity against nucleosomes. [provided by RefSeq, Aug 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032482.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOT1L	NM_032482.3	MANE Select	c.201-796A>G		intron	N/A	NP_115871.1	Q8TEK3-2
	DOT1L	NM_001411141.1		c.201-796A>G		intron	N/A	NP_001398070.1	A0A8I5QL06

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOT1L	ENST00000398665.8	TSL:1 MANE Select	c.201-796A>G		intron	N/A	ENSP00000381657.3	Q8TEK3-2
	DOT1L	ENST00000686010.1		c.201-796A>G		intron	N/A	ENSP00000510335.1	A0A8I5QL06
	DOT1L	ENST00000936177.1		c.201-796A>G		intron	N/A	ENSP00000606236.1

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128327 AN: 152066 Hom.: 54931 Cov.: 33

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.906

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.899

Gnomad FIN AF: 0.936

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.918

Gnomad OTH AF: 0.865

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

GnomAD4 genome AF: 0.844 AC: 128387 AN: 152184 Hom.: 54945 Cov.: 33 AF XY: 0.845 AC XY: 62909 AN XY: 74414

African (AFR) AF: 0.697 AC: 28928 AN: 41494

American (AMR) AF: 0.816 AC: 12479 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.927 AC: 3219 AN: 3472

East Asian (EAS) AF: 0.804 AC: 4147 AN: 5160

South Asian (SAS) AF: 0.899 AC: 4344 AN: 4830

European-Finnish (FIN) AF: 0.936 AC: 9927 AN: 10610

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.918 AC: 62444 AN: 68008

Other (OTH) AF: 0.858 AC: 1809 AN: 2108

Alfa AF: 0.881 Hom.: 9141

Bravo AF: 0.827

Asia WGS AF: 0.806 AC: 2804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.27
DANN	Benign	0.19
PhyloP100		-4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs8113528; hg19: chr19-2188935;