rs16853574

chr3-169361975-T-C

Variant summary

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

The NM_004991.4(MECOM):c.375+19212A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0483 in 151,998 control chromosomes in the GnomAD database, including 218 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 0.048 (218 hom., cov: 32)
• Consequence: MECOM NM_004991.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MECOM	NM_004991.4	c.375+19212A>G		intron_variant		ENST00000651503.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MECOM	ENST00000651503.2	c.375+19212A>G		intron_variant			NM_004991.4	P3
MECOM	ENST00000485957.1	n.621+19212A>G		intron_variant, non_coding_transcript_variant		1
MECOM	ENST00000494292.6	c.375+19212A>G		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.0483 AC: 7336 AN: 151880 Hom.: 216 Cov.: 32

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0615

Gnomad ASJ AF: 0.0188

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0341

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0532

Gnomad OTH AF: 0.0594

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

GnomAD4 genome AF: 0.0483 AC: 7343 AN: 151998 Hom.: 218 Cov.: 32 AF XY: 0.0468 AC XY: 3473 AN XY: 74268

Gnomad4 AFR AF: 0.0380

Gnomad4 AMR AF: 0.0619

Gnomad4 ASJ AF: 0.0188

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.0220

Gnomad4 FIN AF: 0.0341

Gnomad4 NFE AF: 0.0532

Gnomad4 OTH AF: 0.0593

Alfa AF: 0.0507 Hom.: 254

Bravo AF: 0.0518

Asia WGS AF: 0.0670 AC: 231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.048
Dann	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16853574; hg19: chr3-169079763;