rs3807348

Positions:

• chr7-130496266-G-A
• chr7-130496266-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002402.4(MEST):​c.181+744G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 426,802 control chromosomes in the GnomAD database, including 57,790 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 0.47 (18269 hom., cov: 32)
  • Exomes 𝑓: 0.53 (39521 hom.)
• Consequence: MEST NM_002402.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEST	NM_002402.4	c.181+744G>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+744G>A		intron_variant		1	NM_002402.4	ENSP00000223215.4

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71687 AN: 151894 Hom.: 18254 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.483

GnomAD4 exome AF: 0.533 AC: 146482 AN: 274790 Hom.: 39521 Cov.: 0 AF XY: 0.528 AC XY: 83680 AN XY: 158536

Gnomad4 AFR exome AF: 0.254

Gnomad4 AMR exome AF: 0.543

Gnomad4 ASJ exome AF: 0.522

Gnomad4 EAS exome AF: 0.602

Gnomad4 SAS exome AF: 0.484

Gnomad4 FIN exome AF: 0.564

Gnomad4 NFE exome AF: 0.554

Gnomad4 OTH exome AF: 0.531

GnomAD4 genome AF: 0.472 AC: 71740 AN: 152012 Hom.: 18269 Cov.: 32 AF XY: 0.474 AC XY: 35228 AN XY: 74286

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.597

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.481

Alfa AF: 0.314 Hom.: 812

Bravo AF: 0.464

Asia WGS AF: 0.551 AC: 1913 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.45
DANN	Benign	0.36

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: rs3807348; hg19: chr7-130136107; COSMIC: COSV56230456; COSMIC: COSV56230456;