rs6444857

Positions:

• chr3-169520924-G-A
• chr3-169520924-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.38-139400C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,146 control chromosomes in the GnomAD database, including 4,222 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 0.21 (4222 hom., cov: 32)
• Consequence: MECOM NM_004991.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.408

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=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MECOM	NM_004991.4	c.38-139400C>T		intron_variant		ENST00000651503.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MECOM	ENST00000651503.2	c.38-139400C>T		intron_variant			NM_004991.4	P3
MECOM	ENST00000485957.1	n.284-139400C>T		intron_variant, non_coding_transcript_variant		1
MECOM	ENST00000486748.2	c.109+45045C>T		intron_variant		5
MECOM	ENST00000494292.6	c.38-139400C>T		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32436 AN: 152028 Hom.: 4225 Cov.: 32

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.213 AC: 32421 AN: 152146 Hom.: 4222 Cov.: 32 AF XY: 0.211 AC XY: 15673 AN XY: 74372

Gnomad4 AFR AF: 0.0734

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.229

Alfa AF: 0.265 Hom.: 1238

Bravo AF: 0.205

Asia WGS AF: 0.137 AC: 479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.5
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6444857; hg19: chr3-169238712;