rs1537073

Variant names:

• chr9-20528548-A-G
• rs1537073
• NM_004529.4:c.194-71762T>C

Variant summary

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

The NM_004529.4(MLLT3):​c.194-71762T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 152,124 control chromosomes in the GnomAD database, including 19,802 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 0.51 (19802 hom., cov: 33)
• Consequence: MLLT3 NM_004529.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900
• Publications: 0 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLLT3	NM_004529.4	c.194-71762T>C		intron_variant	Intron 2 of 10	ENST00000380338.9	NP_004520.2
MLLT3	NM_001286691.2	c.185-71762T>C		intron_variant	Intron 2 of 10		NP_001273620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLLT3	ENST00000380338.9	c.194-71762T>C		intron_variant	Intron 2 of 10	1	NM_004529.4	ENSP00000369695.4
MLLT3	ENST00000630269.2	c.185-71762T>C		intron_variant	Intron 2 of 10	2		ENSP00000485996.1
MLLT3	ENST00000475957.1	n.377+92106T>C		intron_variant	Intron 2 of 4	2

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76768 AN: 152006 Hom.: 19784 Cov.: 33

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.505 AC: 76829 AN: 152124 Hom.: 19802 Cov.: 33 AF XY: 0.513 AC XY: 38137 AN XY: 74332

African (AFR) AF: 0.548 AC: 22743 AN: 41488

American (AMR) AF: 0.529 AC: 8079 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1852 AN: 3472

East Asian (EAS) AF: 0.688 AC: 3553 AN: 5164

South Asian (SAS) AF: 0.533 AC: 2573 AN: 4824

European-Finnish (FIN) AF: 0.601 AC: 6359 AN: 10584

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30125 AN: 67992

Other (OTH) AF: 0.504 AC: 1064 AN: 2110

Alfa AF: 0.464 Hom.: 20486

Bravo AF: 0.502

Asia WGS AF: 0.569 AC: 1976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.64
PhyloP100		-0.090
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: rs1537073; hg19: chr9-20528546; COSMIC: COSV63496058; COSMIC: COSV63496058;