rs7084454

Positions:

• chr10-21532345-G-A

Variant summary

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

The ENST00000631589.1(MLLT10):​c.1-2300G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 151,948 control chromosomes in the GnomAD database, including 8,481 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 0.32 (8481 hom., cov: 32)
• Consequence: MLLT10 ENST00000631589.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.601

Genes affected

MLLT10 (HGNC:16063): (MLLT10 histone lysine methyltransferase DOT1L cofactor) This gene encodes a transcription factor and has been identified as a partner gene involved in several chromosomal rearrangements resulting in various leukemias. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLLT10	ENST00000631589.1	c.1-2300G>A		intron_variant		5		ENSP00000488569	P1
MLLT10	ENST00000651097.1	c.-197-6488G>A		intron_variant				ENSP00000498343

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49191 AN: 151828 Hom.: 8458 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.0140

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.324 AC: 49263 AN: 151948 Hom.: 8481 Cov.: 32 AF XY: 0.319 AC XY: 23678 AN XY: 74256

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.0139

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.374

Alfa AF: 0.323 Hom.: 1072

Bravo AF: 0.325

Asia WGS AF: 0.167 AC: 580 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	15
DANN	Benign	0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7084454; hg19: chr10-21821274;