rs4245909

Variant names:

• chr3-169455000-A-G
• rs4245909
• NM_004991.4:c.38-73476T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-169455000-A-G
• chr3-169455000-A-T

Variant summary

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

The NM_004991.4(MECOM):​c.38-73476T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,976 control chromosomes in the GnomAD database, including 21,053 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 0.52 (21053 hom., cov: 32)
• Consequence: MECOM NM_004991.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• Publications: 10 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=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MECOM	NM_004991.4	c.38-73476T>C		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.38-73476T>C		intron_variant	Intron 1 of 16		NM_004991.4	ENSP00000498411.1

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79078 AN: 151858 Hom.: 21013 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.521 AC: 79167 AN: 151976 Hom.: 21053 Cov.: 32 AF XY: 0.522 AC XY: 38777 AN XY: 74278

African (AFR) AF: 0.507 AC: 21015 AN: 41424

American (AMR) AF: 0.617 AC: 9422 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1133 AN: 3464

East Asian (EAS) AF: 0.830 AC: 4290 AN: 5168

South Asian (SAS) AF: 0.490 AC: 2356 AN: 4812

European-Finnish (FIN) AF: 0.495 AC: 5226 AN: 10550

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34174 AN: 67972

Other (OTH) AF: 0.525 AC: 1108 AN: 2110

Alfa AF: 0.500 Hom.: 31569

Bravo AF: 0.533

Asia WGS AF: 0.641 AC: 2226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.68
PhyloP100		1.7
Mutation Taster		=97/3	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4245909; hg19: chr3-169172788;