rs28377352

Variant names:

• chr15-89751058-T-G
• rs28377352
• NM_018670.4:c.174A>C

Your query was ambiguous. Multiple possible variants found:

• chr15-89751058-T-G
• chr15-89751058-T-A

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.174A>C​(p.Pro58Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,302,904 control chromosomes in the GnomAD database, including 51,264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6785 hom., cov: 34)
  • Exomes 𝑓: 0.27 (44479 hom.)
• Consequence: MESP1 NM_018670.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.118
• Publications: 8 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=-0.83).
• BP6: Variant 15-89751058-T-G is Benign according to our data. Variant chr15-89751058-T-G is described in ClinVar as Benign. ClinVar VariationId is 1600319.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.118 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 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.174A>C	p.Pro58Pro	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.174A>C	p.Pro58Pro	synonymous	Exon 1 of 2	ENSP00000300057.4	Q9BRJ9
	MESP1	ENST00000559894.1	TSL:2	n.80A>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44157 AN: 150992 Hom.: 6771 Cov.: 34

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.224

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.266

GnomAD2 exomes AF: 0.0448 AC: 515 AN: 11500 AF XY: 0.0480

Gnomad AFR exome AF: 0.0748

Gnomad AMR exome AF: 0.00883

Gnomad ASJ exome AF: 0.00862

Gnomad EAS exome AF: 0.00871

Gnomad FIN exome AF: 0.0434

Gnomad NFE exome AF: 0.0559

Gnomad OTH exome AF: 0.0489

GnomAD4 exome AF: 0.272 AC: 313567 AN: 1151804 Hom.: 44479 Cov.: 57 AF XY: 0.270 AC XY: 149641 AN XY: 554192

African (AFR) AF: 0.383 AC: 8981 AN: 23428

American (AMR) AF: 0.174 AC: 1632 AN: 9364

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 3461 AN: 15492

East Asian (EAS) AF: 0.164 AC: 4525 AN: 27654

South Asian (SAS) AF: 0.216 AC: 8252 AN: 38166

European-Finnish (FIN) AF: 0.181 AC: 4921 AN: 27224

Middle Eastern (MID) AF: 0.237 AC: 804 AN: 3396

European-Non Finnish (NFE) AF: 0.280 AC: 268737 AN: 960092

Other (OTH) AF: 0.261 AC: 12254 AN: 46988

GnomAD4 genome AF: 0.293 AC: 44203 AN: 151100 Hom.: 6785 Cov.: 34 AF XY: 0.286 AC XY: 21139 AN XY: 73872

African (AFR) AF: 0.391 AC: 16137 AN: 41302

American (AMR) AF: 0.218 AC: 3322 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 846 AN: 3464

East Asian (EAS) AF: 0.130 AC: 665 AN: 5116

South Asian (SAS) AF: 0.295 AC: 1417 AN: 4804

European-Finnish (FIN) AF: 0.190 AC: 1985 AN: 10432

Middle Eastern (MID) AF: 0.221 AC: 64 AN: 290

European-Non Finnish (NFE) AF: 0.278 AC: 18751 AN: 67488

Other (OTH) AF: 0.263 AC: 552 AN: 2102

Alfa AF: 0.271 Hom.: 691

Bravo AF: 0.294

Asia WGS AF: 0.219 AC: 760 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
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.5
DANN	Benign	0.56
PhyloP100		0.12
PromoterAI		0.072	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs28377352; hg19: chr15-90294289; COSMIC: COSV55588428; COSMIC: COSV55588428;