rs4245909

chr3-169455000-A-Gchr3-169455000-A-T

Variant summary

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

The NM_004991.4(MECOM):c.38-73476T>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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MECOM	NM_004991.4	c.38-73476T>C		intron_variant		ENST00000651503.2
MECOM-AS1	NR_134932.1	n.69+7065A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MECOM	ENST00000651503.2	c.38-73476T>C		intron_variant			NM_004991.4	P3
MECOM-AS1	ENST00000480669.1	n.69+7065A>G		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.507

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.830

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.525

Alfa AF: 0.496 Hom.: 24171

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4245909; hg19: chr3-169172788;