rs9883650

Variant names:

• chr3-169362397-T-G
• rs9883650
• NM_004991.4:c.375+18790A>C

Variant summary

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

The NM_004991.4(MECOM):​c.375+18790A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 151,872 control chromosomes in the GnomAD database, including 949 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 0.10 (949 hom., cov: 32)
• Consequence: MECOM NM_004991.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.960

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MECOM	NM_004991.4	c.375+18790A>C		intron_variant	Intron 2 of 16	ENST00000651503.2	NP_004982.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MECOM	ENST00000651503.2	c.375+18790A>C		intron_variant	Intron 2 of 16		NM_004991.4	ENSP00000498411.1
MECOM	ENST00000485957.1	n.621+18790A>C		intron_variant	Intron 2 of 2	1
MECOM	ENST00000494292.6	c.375+18790A>C		intron_variant	Intron 2 of 15	5		ENSP00000417899.1

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15201 AN: 151754 Hom.: 946 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0953

Gnomad ASJ AF: 0.0364

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.0402

Gnomad FIN AF: 0.0464

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0740

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.100 AC: 15232 AN: 151872 Hom.: 949 Cov.: 32 AF XY: 0.0985 AC XY: 7313 AN XY: 74230

Gnomad4 AFR AF: 0.158 AC: 0.158099 AN: 0.158099

Gnomad4 AMR AF: 0.0955 AC: 0.0955351 AN: 0.0955351

Gnomad4 ASJ AF: 0.0364 AC: 0.0363531 AN: 0.0363531

Gnomad4 EAS AF: 0.222 AC: 0.22194 AN: 0.22194

Gnomad4 SAS AF: 0.0404 AC: 0.0404229 AN: 0.0404229

Gnomad4 FIN AF: 0.0464 AC: 0.0464218 AN: 0.0464218

Gnomad4 NFE AF: 0.0740 AC: 0.074043 AN: 0.074043

Gnomad4 OTH AF: 0.104 AC: 0.103791 AN: 0.103791

Alfa AF: 0.0846 Hom.: 2755

Bravo AF: 0.109

Asia WGS AF: 0.130 AC: 452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Benign	0.73
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9883650; hg19: chr3-169080185;