rs28368490

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018670.4(MESP1):c.182T>G(p.Leu61Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,317,352 control chromosomes in the GnomAD database, including 41,669 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5827 hom., cov: 34)

Exomes 𝑓: 0.24 ( 35842 hom. )

Consequence

MESP1
NM_018670.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.79

Publications

12 publications found

Variant links:

Genes affected

MESP1 (HGNC:29658): (mesoderm posterior bHLH transcription factor 1) Enables DNA-binding transcription factor activity and transcription cis-regulatory region binding activity. Involved in several processes, including endothelial cell differentiation; heart development; and positive regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MESP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005183816).

BP6

Variant 15-89751050-A-C is Benign according to our data. Variant chr15-89751050-A-C is described in ClinVar as [Benign]. Clinvar id is 1548747.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MESP1	NM_018670.4 link	c.182T>G	p.Leu61Arg	missense_variant	Exon 1 of 2	ENST00000300057.5	NP_061140.1	Q9BRJ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MESP1	ENST00000300057.5 link	c.182T>G	p.Leu61Arg	missense_variant	Exon 1 of 2	1	NM_018670.4	ENSP00000300057.4		Q9BRJ9
MESP1	ENST00000559894.1 link	n.88T>G		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.269

AC:

40639

AN:

151196

Hom.:

5821

Cov.:

show subpopulations

Gnomad AFR

AF:

0.370

Gnomad AMI

AF:

0.481

Gnomad AMR

AF:

0.209

Gnomad ASJ

AF:

0.243

Gnomad EAS

AF:

0.123

Gnomad SAS

AF:

0.288

Gnomad FIN

AF:

0.147

Gnomad MID

AF:

0.221

Gnomad NFE

AF:

0.249

Gnomad OTH

AF:

0.250

GnomAD2 exomes

AF:

0.0267

AC:

218

AN:

8172

AF XY:

0.0268

show subpopulations

Gnomad AFR exome

AF:

0.0907

Gnomad AMR exome

AF:

0.00690

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00643

Gnomad FIN exome

AF:

0.00645

Gnomad NFE exome

AF:

0.0286

Gnomad OTH exome

AF:

0.0156

GnomAD4 exome

AF:

0.242

AC:

281777

AN:

1166050

Hom.:

35842

Cov.:

AF XY:

0.239

AC XY:

134631

AN XY:

562464

show subpopulations

African (AFR)

AF:

0.365

AC:

8563

AN:

23446

American (AMR)

AF:

0.172

AC:

1578

AN:

9158

Ashkenazi Jewish (ASJ)

AF:

0.221

AC:

3467

AN:

15712

East Asian (EAS)

AF:

0.147

AC:

4051

AN:

27594

South Asian (SAS)

AF:

0.204

AC:

8202

AN:

40144

European-Finnish (FIN)

AF:

0.143

AC:

3931

AN:

27580

Middle Eastern (MID)

AF:

0.229

AC:

797

AN:

3480

European-Non Finnish (NFE)

AF:

0.247

AC:

239883

AN:

971392

Other (OTH)

AF:

0.238

AC:

11305

AN:

47544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.414

Heterozygous variant carriers

12894

25787

38681

51574

64468

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.269

AC:

40667

AN:

151302

Hom.:

5827

Cov.:

AF XY:

0.262

AC XY:

19362

AN XY:

73958

show subpopulations

African (AFR)

AF:

0.370

AC:

15247

AN:

41226

American (AMR)

AF:

0.209

AC:

3181

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.243

AC:

839

AN:

3458

East Asian (EAS)

AF:

0.123

AC:

627

AN:

5090

South Asian (SAS)

AF:

0.287

AC:

1379

AN:

4806

European-Finnish (FIN)

AF:

0.147

AC:

1538

AN:

10486

Middle Eastern (MID)

AF:

0.221

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.249

AC:

16842

AN:

67704

Other (OTH)

AF:

0.247

AC:

520

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1495

2989

4484

5978

7473

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.257

Hom.:

629

Bravo

AF:

0.273

ExAC

AF:

0.0179

AC:

1401

Asia WGS

AF:

0.211

AC:

731

AN:

3452

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

MESP1-related disorder

Benign:1

Nov 11, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.042

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.37

(source)

DANN

Benign

0.24

DEOGEN2

Benign

0.089

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.16

MetaRNN

Benign

0.0052

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

PhyloP100

-2.8

PrimateAI

Uncertain

0.74

PROVEAN

Benign

0.32

REVEL

Benign

0.097

Sift

Benign

0.48

Sift4G

Benign

0.45

Polyphen

0.0

Vest4

0.028

MPC

0.65

ClinPred

0.0040

GERP RS

-1.6

PromoterAI

0.026

Neutral

(source)

Varity_R

0.080

gMVP

0.22

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs28368490

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over