rs784288

Positions:

• chr3-169253443-A-G
• chr3-169253443-A-T

Variant summary

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

The NM_004991.4(MECOM):​c.376-109611T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 150,508 control chromosomes in the GnomAD database, including 18,921 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 0.49 (18921 hom., cov: 29)
• Consequence: MECOM NM_004991.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MECOM	NM_004991.4	c.376-109611T>C		intron_variant		ENST00000651503.2	NP_004982.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MECOM	ENST00000651503.2	c.376-109611T>C		intron_variant			NM_004991.4	ENSP00000498411	P3
MECOM	ENST00000485957.1	n.622-103688T>C		intron_variant, non_coding_transcript_variant		1
MECOM	ENST00000481315.1	c.-190+15692T>C		intron_variant		5		ENSP00000418046
MECOM	ENST00000494292.6	c.376-109611T>C		intron_variant		5		ENSP00000417899	A1

Frequencies

GnomAD3 genomes AF: 0.490 AC: 73692 AN: 150422 Hom.: 18909 Cov.: 29

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.490 AC: 73734 AN: 150508 Hom.: 18921 Cov.: 29 AF XY: 0.494 AC XY: 36295 AN XY: 73428

Gnomad4 AFR AF: 0.621

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.708

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.439

Alfa AF: 0.449 Hom.: 5577

Bravo AF: 0.501

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.3
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs784288; hg19: chr3-168971231;