rs2305441

Variant names:

• chr15-89750545-A-C
• rs2305441
• NM_018670.4:c.687T>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018670.4(MESP1):​c.687T>G​(p.Pro229Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 1,481,144 control chromosomes in the GnomAD database, including 296,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (33519 hom., cov: 35)
  • Exomes 𝑓: 0.62 (262530 hom.)
• Consequence: MESP1 NM_018670.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -4.22
• Publications: 14 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 15-89750545-A-C is Benign according to our data. Variant chr15-89750545-A-C is described in ClinVar as Benign. ClinVar VariationId is 1601156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.22 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.812 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.687T>G	p.Pro229Pro	synonymous	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.687T>G	p.Pro229Pro	synonymous	Exon 1 of 2	ENSP00000300057.4	Q9BRJ9
	MESP1	ENST00000559894.1	TSL:2	n.115-318T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98630 AN: 151894 Hom.: 33486 Cov.: 35

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.682

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.647

GnomAD2 exomes AF: 0.549 AC: 55024 AN: 100312 AF XY: 0.562

Gnomad AFR exome AF: 0.801

Gnomad AMR exome AF: 0.382

Gnomad ASJ exome AF: 0.679

Gnomad EAS exome AF: 0.275

Gnomad FIN exome AF: 0.465

Gnomad NFE exome AF: 0.621

Gnomad OTH exome AF: 0.577

GnomAD4 exome AF: 0.623 AC: 828268 AN: 1329138 Hom.: 262530 Cov.: 56 AF XY: 0.624 AC XY: 407468 AN XY: 652522

African (AFR) AF: 0.832 AC: 23649 AN: 28410

American (AMR) AF: 0.403 AC: 11610 AN: 28828

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 14341 AN: 20222

East Asian (EAS) AF: 0.278 AC: 9849 AN: 35406

South Asian (SAS) AF: 0.656 AC: 45445 AN: 69288

European-Finnish (FIN) AF: 0.491 AC: 15752 AN: 32060

Middle Eastern (MID) AF: 0.762 AC: 3533 AN: 4634

European-Non Finnish (NFE) AF: 0.634 AC: 669526 AN: 1055476

Other (OTH) AF: 0.631 AC: 34563 AN: 54814

GnomAD4 genome AF: 0.649 AC: 98713 AN: 152006 Hom.: 33519 Cov.: 35 AF XY: 0.635 AC XY: 47177 AN XY: 74266

African (AFR) AF: 0.820 AC: 34052 AN: 41550

American (AMR) AF: 0.511 AC: 7814 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 2494 AN: 3470

East Asian (EAS) AF: 0.276 AC: 1407 AN: 5104

South Asian (SAS) AF: 0.636 AC: 3071 AN: 4830

European-Finnish (FIN) AF: 0.470 AC: 4963 AN: 10564

Middle Eastern (MID) AF: 0.678 AC: 198 AN: 292

European-Non Finnish (NFE) AF: 0.628 AC: 42672 AN: 67896

Other (OTH) AF: 0.644 AC: 1357 AN: 2106

Alfa AF: 0.632 Hom.: 6729

Bravo AF: 0.659

Asia WGS AF: 0.486 AC: 1691 AN: 3470

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
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.43
PhyloP100		-4.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2305441; hg19: chr15-90293776;