rs448378

Positions:

• chr3-169383111-G-A
• chr3-169383111-G-C
• chr3-169383111-G-T

Variant summary

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

The NM_004991.4(MECOM):​c.38-1587C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 151,756 control chromosomes in the GnomAD database, including 22,034 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 0.53 (22034 hom., cov: 30)
• Consequence: MECOM NM_004991.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MECOM	NM_004991.4	c.38-1587C>T		intron_variant		ENST00000651503.2	NP_004982.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MECOM	ENST00000651503.2	c.38-1587C>T		intron_variant			NM_004991.4	ENSP00000498411	P3
MECOM	ENST00000485957.1	n.284-1587C>T		intron_variant, non_coding_transcript_variant		1
MECOM	ENST00000486748.2	c.110-1587C>T		intron_variant		5		ENSP00000419537
MECOM	ENST00000494292.6	c.38-1587C>T		intron_variant		5		ENSP00000417899	A1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80886 AN: 151638 Hom.: 22006 Cov.: 30

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.534 AC: 80962 AN: 151756 Hom.: 22034 Cov.: 30 AF XY: 0.537 AC XY: 39860 AN XY: 74172

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.615

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.535

Alfa AF: 0.531 Hom.: 28750

Bravo AF: 0.538

Asia WGS AF: 0.656 AC: 2279 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs448378; hg19: chr3-169100899;