Genetic Variant MLLT11:p.Thr71Thr (chr1-151067437-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_006818.4(MLLT11):c.213C>T(p.Thr71Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00474 in 1,614,138 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0049 ( 29 hom. )

Consequence

MLLT11
NM_006818.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.74

Variant links:

Genes affected

MLLT11 (HGNC:16997): (MLLT11 transcription factor 7 cofactor) The gene variously symbolized ALL1, HRX, or MLL located on 11q23 has been demonstrated to be fused with a number of translocation partners in cases of leukemia. t(1;11)(q21;q23) translocations that fused the MLL gene to a gene on chromosomal band 1q21 in 2 infants with acute myelomonocytic leukemia have been demonstrated. The N-terminal portion of the MLL gene is critical for leukemogenesis in translocations involving band 11q23. This gene encodes 90 amino acids. It was found to be highly expressed in the thymus but not in peripheral lymphoid tissues. In contrast to its restricted distribution in normal hematopoietic tissue, this gene was expressed in all leukemic cell lines tested. [provided by RefSeq, Jul 2008]

MLLT11 links:

CDC42SE1 (HGNC:17719): (CDC42 small effector 1) Predicted to enable GTPase inhibitor activity. Predicted to be involved in signal transduction. Located in cell junction. [provided by Alliance of Genome Resources, Apr 2022]

CDC42SE1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 1-151067437-C-T is Benign according to our data. Variant chr1-151067437-C-T is described in ClinVar as [Benign]. Clinvar id is 708650.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.74 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLLT11	NM_006818.4 link	c.213C>T	p.Thr71Thr	synonymous_variant	Exon 2 of 2	ENST00000368921.5	NP_006809.1	Q13015Q6FGF7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLLT11	ENST00000368921.5 link	c.213C>T	p.Thr71Thr	synonymous_variant	Exon 2 of 2	1	NM_006818.4	ENSP00000357917.3		Q13015
CDC42SE1	ENST00000439374.6 link	c.-761-103G>A		intron_variant	Intron 2 of 7	5		ENSP00000475845.1		Q9NRR8-1

Frequencies

GnomAD3 genomes

AF:

0.00324

AC:

493

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000773

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00367

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00807

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00489

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00394

AC:

990

AN:

251470

AF XY:

0.00443

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00205

Gnomad ASJ exome

AF:

0.00367

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00531

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00489

AC:

7152

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00500

AC XY:

3636

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

AC:

AN:

33480

Gnomad4 AMR exome

AF:

0.00192

AC:

AN:

44724

Gnomad4 ASJ exome

AF:

0.00386

AC:

101

AN:

26136

Gnomad4 EAS exome

AF:

0.0000252

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.00754

AC:

650

AN:

86258

Gnomad4 FIN exome

AF:

0.000505

AC:

AN:

53418

Gnomad4 NFE exome

AF:

0.00533

AC:

5926

AN:

1112010

Gnomad4 Remaining exome

AF:

0.00459

AC:

277

AN:

60396

Heterozygous variant carriers

414

828

1243

1657

2071

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

208

416

624

832

1040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00324

AC:

494

AN:

152252

Hom.:

Cov.:

AF XY:

0.00304

AC XY:

226

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000771

AC:

0.000770564

AN:

0.000770564

Gnomad4 AMR

AF:

0.00367

AC:

0.0036654

AN:

0.0036654

Gnomad4 ASJ

AF:

0.00518

AC:

0.00518433

AN:

0.00518433

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00829

AC:

0.008285

AN:

0.008285

Gnomad4 FIN

AF:

0.000377

AC:

0.000377003

AN:

0.000377003

Gnomad4 NFE

AF:

0.00489

AC:

0.0048949

AN:

0.0048949

Gnomad4 OTH

AF:

0.00425

AC:

0.00425331

AN:

0.00425331

Heterozygous variant carriers

109

136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00443

Hom.:

Bravo

AF:

0.00332

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00556

EpiControl

AF:

0.00492

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.77

Mutation Taster

=97/3

polymorphism

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over