rs7868612

Variant names:

• chr9-20616619-G-A
• rs7868612
• NM_004529.4:c.193+4035C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-20616619-G-A
• chr9-20616619-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.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 NM_004529.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• 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=-0.95).
• 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 rank	MANE	Protein	UniProt
MLLT3	NM_004529.4	c.193+4035C>T		intron_variant	Intron 2 of 10	ENST00000380338.9	NP_004520.2
MLLT3	NM_001286691.2	c.184+4035C>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.193+4035C>T		intron_variant	Intron 2 of 10	1	NM_004529.4	ENSP00000369695.4
MLLT3	ENST00000630269.2	c.184+4035C>T		intron_variant	Intron 2 of 10	2		ENSP00000485996.1
MLLT3	ENST00000475957.1	n.377+4035C>T		intron_variant	Intron 2 of 4	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

African (AFR) AF: 0.276 AC: 11458 AN: 41476

American (AMR) AF: 0.420 AC: 6411 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1805 AN: 3466

East Asian (EAS) AF: 0.314 AC: 1620 AN: 5164

South Asian (SAS) AF: 0.499 AC: 2408 AN: 4826

European-Finnish (FIN) AF: 0.547 AC: 5778 AN: 10556

Middle Eastern (MID) AF: 0.517 AC: 151 AN: 292

European-Non Finnish (NFE) AF: 0.504 AC: 34200 AN: 67892

Other (OTH) AF: 0.431 AC: 906 AN: 2102

Alfa AF: 0.446 Hom.: 9069

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
PhyloP100		-2.0
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: rs7868612; hg19: chr9-20616618;