rs7868612

Positions:

• chr9-20616619-G-A
• chr9-20616619-G-T

Variant summary

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

The ENST00000380338.9(MLLT3):​c.193+4035C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,960 control chromosomes in the GnomAD database, including 14,929 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 0.43 (14929 hom., cov: 33)
• Consequence: MLLT3 ENST00000380338.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLLT3	NM_004529.4	c.193+4035C>T		intron_variant		ENST00000380338.9	NP_004520.2
MLLT3	NM_001286691.2	c.184+4035C>T		intron_variant			NP_001273620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLLT3	ENST00000380338.9	c.193+4035C>T		intron_variant		1	NM_004529.4	ENSP00000369695	P4
MLLT3	ENST00000630269.2	c.184+4035C>T		intron_variant		2		ENSP00000485996	A1
MLLT3	ENST00000475957.1	n.377+4035C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65376 AN: 151842 Hom.: 14931 Cov.: 33

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.430 AC: 65379 AN: 151960 Hom.: 14929 Cov.: 33 AF XY: 0.433 AC XY: 32165 AN XY: 74236

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.499

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.431

Alfa AF: 0.435 Hom.: 4040

Bravo AF: 0.410

Asia WGS AF: 0.396 AC: 1377 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.024
DANN	Benign	0.53

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: rs7868612; hg19: chr9-20616618;