rs41272366

Positions:

• chr7-130496224-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002402.4(MEST):​c.181+702T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.02 in 450,364 control chromosomes in the GnomAD database, including 145 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 0.015 (33 hom., cov: 31)
  • Exomes 𝑓: 0.022 (112 hom.)
• Consequence: MEST NM_002402.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.79

Genes affected

MEST (HGNC:7028): (mesoderm specific transcript) This gene encodes a member of the alpha/beta hydrolase superfamily. It is imprinted, exhibiting preferential expression from the paternal allele in fetal tissues, and isoform-specific imprinting in lymphocytes. The loss of imprinting of this gene has been linked to certain types of cancer and may be due to promotor switching. The encoded protein may play a role in development. Alternatively spliced transcript variants encoding multiple isoforms have been identified for this gene. Pseudogenes of this gene are located on the short arm of chromosomes 3 and 4, and the long arm of chromosomes 6 and 15. [provided by RefSeq, Dec 2011]

ENSG00000270823 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0154 (2351/152342) while in subpopulation SAS AF= 0.0378 (182/4816). AF 95% confidence interval is 0.0333. There are 33 homozygotes in gnomad4. There are 1139 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2351 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEST	NM_002402.4	c.181+702T>A		intron_variant		ENST00000223215.10	NP_002393.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEST	ENST00000223215.10	c.181+702T>A		intron_variant		1	NM_002402.4	ENSP00000223215.4

Frequencies

GnomAD3 genomes AF: 0.0154 AC: 2351 AN: 152224 Hom.: 33 Cov.: 31

Gnomad AFR AF: 0.00405

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0373

Gnomad FIN AF: 0.00923

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0211

Gnomad OTH AF: 0.0172

GnomAD3 exomes AF: 0.0194 AC: 2629 AN: 135616 Hom.: 40 AF XY: 0.0215 AC XY: 1547 AN XY: 71950

Gnomad AFR exome AF: 0.00365

Gnomad AMR exome AF: 0.00966

Gnomad ASJ exome AF: 0.0278

Gnomad EAS exome AF: 0.000104

Gnomad SAS exome AF: 0.0438

Gnomad FIN exome AF: 0.00968

Gnomad NFE exome AF: 0.0217

Gnomad OTH exome AF: 0.0174

GnomAD4 exome AF: 0.0223 AC: 6634 AN: 298022 Hom.: 112 Cov.: 0 AF XY: 0.0248 AC XY: 4201 AN XY: 169576

Gnomad4 AFR exome AF: 0.00353

Gnomad4 AMR exome AF: 0.00893

Gnomad4 ASJ exome AF: 0.0301

Gnomad4 EAS exome AF: 0.000121

Gnomad4 SAS exome AF: 0.0430

Gnomad4 FIN exome AF: 0.0110

Gnomad4 NFE exome AF: 0.0203

Gnomad4 OTH exome AF: 0.0194

GnomAD4 genome AF: 0.0154 AC: 2351 AN: 152342 Hom.: 33 Cov.: 31 AF XY: 0.0153 AC XY: 1139 AN XY: 74500

Gnomad4 AFR AF: 0.00404

Gnomad4 AMR AF: 0.0114

Gnomad4 ASJ AF: 0.0280

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0378

Gnomad4 FIN AF: 0.00923

Gnomad4 NFE AF: 0.0211

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0216 Hom.: 5

Bravo AF: 0.0149

Asia WGS AF: 0.0170 AC: 58 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.90

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

Publications

LitVar

Other links and lift over

dbSNP: rs41272366; hg19: chr7-130136065;