rs12495069

chr3-169503316-G-C

Variant summary

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

The NM_004991.4(MECOM):c.38-121792C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,844 control chromosomes in the GnomAD database, including 10,400 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 0.35 (10400 hom., cov: 32)
• Consequence: MECOM NM_004991.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MECOM	NM_004991.4	c.38-121792C>G		intron_variant		ENST00000651503.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MECOM	ENST00000651503.2	c.38-121792C>G		intron_variant			NM_004991.4	P3
MECOM	ENST00000485957.1	n.284-121792C>G		intron_variant, non_coding_transcript_variant		1
MECOM	ENST00000486748.2	c.109+62653C>G		intron_variant		5
MECOM	ENST00000494292.6	c.38-121792C>G		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53065 AN: 151726 Hom.: 10399 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.350 AC: 53091 AN: 151844 Hom.: 10400 Cov.: 32 AF XY: 0.342 AC XY: 25349 AN XY: 74222

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.326

Alfa AF: 0.328 Hom.: 1090

Bravo AF: 0.360

Asia WGS AF: 0.179 AC: 626 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.61
Dann	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12495069; hg19: chr3-169221104;