dbSNP rs16853574: MECOM:c.375+19212A>G (chr3-169361975-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.59

Publications

8 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

MECOM-associated syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
radioulnar synostosis with amegakaryocytic thrombocytopenia 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MECOM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MECOM	NM_004991.4 link	c.375+19212A>G		intron_variant	Intron 2 of 16	ENST00000651503.2	NP_004982.2	Q03112-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MECOM	ENST00000651503.2 link	c.375+19212A>G	intron_variant	Intron 2 of 16		NM_004991.4	ENSP00000498411.1	Q03112-3
MECOM	ENST00000485957.1 link	n.621+19212A>G	intron_variant	Intron 2 of 2	1
MECOM	ENST00000494292.6 link	c.375+19212A>G	intron_variant	Intron 2 of 15	5		ENSP00000417899.1	Q03112-7

Frequencies

GnomAD3 genomes

AF:

0.0483

AC:

7336

AN:

151880

Hom.:

216

Cov.:

show subpopulations

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.:

AF XY:

0.0468

AC XY:

3473

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.0380

AC:

1579

AN:

41528

American (AMR)

AF:

0.0619

AC:

943

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.0188

AC:

AN:

3460

East Asian (EAS)

AF:

0.104

AC:

535

AN:

5120

South Asian (SAS)

AF:

0.0220

AC:

106

AN:

4822

European-Finnish (FIN)

AF:

0.0341

AC:

362

AN:

10612

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0532

AC:

3614

AN:

67898

Other (OTH)

AF:

0.0593

AC:

125

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

355

711

1066

1422

1777

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0523

Hom.:

676

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

(source)

DANN

Benign

0.64

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over