rs6475448

Variant names:

• chr9-20497144-G-A
• rs6475448
• NM_004529.4:c.194-40358C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-20497144-G-A
• chr9-20497144-G-C
• chr9-20497144-G-T

Variant summary

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

The NM_004529.4(MLLT3):​c.194-40358C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 152,128 control chromosomes in the GnomAD database, including 39,049 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 0.71 (39049 hom., cov: 32)
• Consequence: MLLT3 NM_004529.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226
• Publications: 13 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLLT3	NM_004529.4	c.194-40358C>T		intron_variant	Intron 2 of 10	ENST00000380338.9	NP_004520.2
MLLT3	NM_001286691.2	c.185-40358C>T		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.194-40358C>T		intron_variant	Intron 2 of 10	1	NM_004529.4	ENSP00000369695.4
MLLT3	ENST00000630269.2	c.185-40358C>T		intron_variant	Intron 2 of 10	2		ENSP00000485996.1
MLLT3	ENST00000475957.1	n.378-82719C>T		intron_variant	Intron 2 of 4	2

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107931 AN: 152008 Hom.: 39000 Cov.: 32

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.678

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

GnomAD4 genome AF: 0.710 AC: 108040 AN: 152128 Hom.: 39049 Cov.: 32 AF XY: 0.713 AC XY: 53046 AN XY: 74382

African (AFR) AF: 0.847 AC: 35158 AN: 41508

American (AMR) AF: 0.699 AC: 10690 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2147 AN: 3466

East Asian (EAS) AF: 0.788 AC: 4079 AN: 5174

South Asian (SAS) AF: 0.715 AC: 3446 AN: 4822

European-Finnish (FIN) AF: 0.703 AC: 7431 AN: 10576

Middle Eastern (MID) AF: 0.647 AC: 189 AN: 292

European-Non Finnish (NFE) AF: 0.633 AC: 43017 AN: 67972

Other (OTH) AF: 0.682 AC: 1441 AN: 2114

Alfa AF: 0.654 Hom.: 141411

Bravo AF: 0.713

Asia WGS AF: 0.752 AC: 2611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.42
PhyloP100		0.23
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: rs6475448; hg19: chr9-20497142;