chr1-151067437-C-T

Variant names:

• chr1-151067437-C-T
• rs41266626
• NM_006818.4:c.213C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.74
• Publications: 4 publications found

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]

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]

ACMG classification

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 VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006818.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLLT11	NM_006818.4	MANE Select	c.213C>T	p.Thr71Thr	synonymous	Exon 2 of 2	NP_006809.1	Q13015

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLLT11	ENST00000368921.5	TSL:1 MANE Select	c.213C>T	p.Thr71Thr	synonymous	Exon 2 of 2	ENSP00000357917.3	Q13015
	MLLT11	ENST00000889973.1		c.213C>T	p.Thr71Thr	synonymous	Exon 3 of 3	ENSP00000560032.1
	MLLT11	ENST00000889974.1		c.213C>T	p.Thr71Thr	synonymous	Exon 3 of 3	ENSP00000560033.1

Frequencies

GnomAD3 genomes AF: 0.00324 AC: 493 AN: 152134 Hom.: 2 Cov.: 32

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

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.: 29 Cov.: 31 AF XY: 0.00500 AC XY: 3636 AN XY: 727244

African (AFR) AF: 0.000687 AC: 23 AN: 33480

American (AMR) AF: 0.00192 AC: 86 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00386 AC: 101 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00754 AC: 650 AN: 86258

European-Finnish (FIN) AF: 0.000505 AC: 27 AN: 53418

Middle Eastern (MID) AF: 0.0106 AC: 61 AN: 5764

European-Non Finnish (NFE) AF: 0.00533 AC: 5926 AN: 1112010

Other (OTH) AF: 0.00459 AC: 277 AN: 60396

GnomAD4 genome AF: 0.00324 AC: 494 AN: 152252 Hom.: 2 Cov.: 32 AF XY: 0.00304 AC XY: 226 AN XY: 74452

African (AFR) AF: 0.000771 AC: 32 AN: 41528

American (AMR) AF: 0.00367 AC: 56 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00518 AC: 18 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00829 AC: 40 AN: 4828

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10610

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00489 AC: 333 AN: 68030

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.00443 Hom.: 3

Bravo AF: 0.00332

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00556

EpiControl AF: 0.00492

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	13
DANN	Benign	0.77
PhyloP100		1.7
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

Other links and lift over

dbSNP: rs41266626; hg19: chr1-151039913;