rs7867710

Positions:

• chr9-20602189-T-C

Variant summary

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

The NM_004529.4(MLLT3):​c.193+18465A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,016 control chromosomes in the GnomAD database, including 7,683 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 0.31 (7683 hom., cov: 32)
• Consequence: MLLT3 NM_004529.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980

Genes affected

MLLT3 (HGNC:7136): (MLLT3 super elongation complex subunit) Enables chromatin binding activity and lysine-acetylated histone binding activity. Involved in several processes, including hematopoietic stem cell differentiation; positive regulation of transcription, DNA-templated; and regulation of stem cell division. Acts upstream of or within negative regulation of canonical Wnt signaling pathway and positive regulation of Wnt signaling pathway, planar cell polarity pathway. Located in cytosol and nucleoplasm. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLLT3	NM_004529.4	c.193+18465A>G		intron_variant		ENST00000380338.9	NP_004520.2
MLLT3	NM_001286691.2	c.184+18465A>G		intron_variant			NP_001273620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLLT3	ENST00000380338.9	c.193+18465A>G		intron_variant		1	NM_004529.4	ENSP00000369695	P4
MLLT3	ENST00000630269.2	c.184+18465A>G		intron_variant		2		ENSP00000485996	A1
MLLT3	ENST00000475957.1	n.377+18465A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47177 AN: 151898 Hom.: 7678 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.310 AC: 47192 AN: 152016 Hom.: 7683 Cov.: 32 AF XY: 0.316 AC XY: 23449 AN XY: 74280

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.320

Alfa AF: 0.325 Hom.: 1046

Bravo AF: 0.292

Asia WGS AF: 0.376 AC: 1308 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs7867710; hg19: chr9-20602188;