rs28368490

Variant names:

• chr15-89751050-A-C
• rs28368490
• NM_018670.4:c.182T>G

Your query was ambiguous. Multiple possible variants found:

• chr15-89751050-A-C
• chr15-89751050-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.79
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ACMG classification

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018670.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MESP1	NM_018670.4	MANE Select	c.182T>G	p.Leu61Arg	missense	Exon 1 of 2	NP_061140.1	Q9BRJ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MESP1	ENST00000300057.5	TSL:1 MANE Select	c.182T>G	p.Leu61Arg	missense	Exon 1 of 2	ENSP00000300057.4	Q9BRJ9
	MESP1	ENST00000559894.1	TSL:2	n.88T>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40639 AN: 151196 Hom.: 5821 Cov.: 34

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

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.: 56 AF XY: 0.239 AC XY: 134631 AN XY: 562464

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

GnomAD4 genome AF: 0.269 AC: 40667 AN: 151302 Hom.: 5827 Cov.: 34 AF XY: 0.262 AC XY: 19362 AN XY: 73958

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: 64 AN: 290

European-Non Finnish (NFE) AF: 0.249 AC: 16842 AN: 67704

Other (OTH) AF: 0.247 AC: 520 AN: 2108

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	MESP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.042
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.37
DANN	Benign	0.24
DEOGEN2	Benign	0.089	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N
PhyloP100		-2.8
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.32	N
REVEL	Benign	0.097
Sift	Benign	0.48	T
Sift4G	Benign	0.45	T
Polyphen		0.0	B
Vest4		0.028
MPC		0.65
ClinPred		0.0040	T
GERP RS		-1.6
PromoterAI		0.026	Neutral
Varity_R		0.080
gMVP		0.22
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs28368490; hg19: chr15-90294281; COSMIC: COSV55588418; COSMIC: COSV55588418;