rs11880992

Variant names:

• chr19-2176404-G-A
• rs11880992
• NM_032482.3:c.82-4309G>A

Variant summary

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

The NM_032482.3(DOT1L):​c.82-4309G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,990 control chromosomes in the GnomAD database, including 10,387 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 0.36 (10387 hom., cov: 32)
• Consequence: DOT1L NM_032482.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 36 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOT1L	NM_032482.3	c.82-4309G>A		intron_variant	Intron 1 of 27	ENST00000398665.8	NP_115871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOT1L	ENST00000398665.8	c.82-4309G>A		intron_variant	Intron 1 of 27	1	NM_032482.3	ENSP00000381657.3
DOT1L	ENST00000686010.1	c.82-4309G>A		intron_variant	Intron 1 of 27			ENSP00000510335.1
DOT1L	ENST00000452696.5	c.82-4309G>A		intron_variant	Intron 1 of 7	3		ENSP00000404284.1
DOT1L	ENST00000478937.3	n.67-4309G>A		intron_variant	Intron 1 of 5	3		ENSP00000484015.1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55196 AN: 151870 Hom.: 10388 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.363 AC: 55208 AN: 151990 Hom.: 10387 Cov.: 32 AF XY: 0.360 AC XY: 26774 AN XY: 74270

African (AFR) AF: 0.278 AC: 11509 AN: 41452

American (AMR) AF: 0.356 AC: 5435 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1344 AN: 3470

East Asian (EAS) AF: 0.333 AC: 1718 AN: 5158

South Asian (SAS) AF: 0.346 AC: 1671 AN: 4824

European-Finnish (FIN) AF: 0.350 AC: 3699 AN: 10568

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.420 AC: 28523 AN: 67938

Other (OTH) AF: 0.392 AC: 828 AN: 2112

Alfa AF: 0.401 Hom.: 21636

Bravo AF: 0.363

Asia WGS AF: 0.330 AC: 1148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.62
PhyloP100		-1.8
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: rs11880992; hg19: chr19-2176403;