3-169448100-C-T

Variant names:

• chr3-169448100-C-T
• rs1918974
• NM_004991.4:c.38-66576G>A

Variant summary

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

The NM_004991.4(MECOM):​c.38-66576G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 151,888 control chromosomes in the GnomAD database, including 25,496 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 0.57 (25496 hom., cov: 31)
• Consequence: MECOM NM_004991.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.391
• Publications: 28 publications found

Genes affected

MECOM (HGNC:3498): (MDS1 and EVI1 complex locus) The protein encoded by this gene is a transcriptional regulator and oncoprotein that may be involved in hematopoiesis, apoptosis, development, and cell differentiation and proliferation. The encoded protein can interact with CTBP1, SMAD3, CREBBP, KAT2B, MAPK8, and MAPK9. This gene can undergo translocation with the AML1 gene, resulting in overexpression of this gene and the onset of leukemia. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

MECOM-AS1 (HGNC:40368): (MECOM antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MECOM	NM_004991.4	c.38-66576G>A		intron_variant	Intron 1 of 16	ENST00000651503.2	NP_004982.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MECOM	ENST00000651503.2	c.38-66576G>A		intron_variant	Intron 1 of 16		NM_004991.4	ENSP00000498411.1

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87136 AN: 151770 Hom.: 25460 Cov.: 31

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.574 AC: 87223 AN: 151888 Hom.: 25496 Cov.: 31 AF XY: 0.577 AC XY: 42807 AN XY: 74232

African (AFR) AF: 0.594 AC: 24612 AN: 41414

American (AMR) AF: 0.645 AC: 9838 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1370 AN: 3466

East Asian (EAS) AF: 0.901 AC: 4645 AN: 5156

South Asian (SAS) AF: 0.505 AC: 2426 AN: 4806

European-Finnish (FIN) AF: 0.578 AC: 6092 AN: 10544

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.538 AC: 36582 AN: 67934

Other (OTH) AF: 0.572 AC: 1204 AN: 2104

Alfa AF: 0.567 Hom.: 8807

Bravo AF: 0.583

Asia WGS AF: 0.686 AC: 2385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.9
DANN	Benign	0.20
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1918974; hg19: chr3-169165888;