rs2301335

Positions:

• chr7-130492985-G-A

Variant summary

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

The NM_002402.4(MEST):​c.26+646G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 151,836 control chromosomes in the GnomAD database, including 17,889 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 0.46 (17889 hom., cov: 30)
• Consequence: MEST NM_002402.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEST	NM_002402.4	c.26+646G>A		intron_variant		ENST00000223215.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEST	ENST00000223215.10	c.26+646G>A		intron_variant		1	NM_002402.4

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70372 AN: 151718 Hom.: 17881 Cov.: 30

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.478

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.464 AC: 70416 AN: 151836 Hom.: 17889 Cov.: 30 AF XY: 0.466 AC XY: 34577 AN XY: 74156

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.565

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.475

Alfa AF: 0.495 Hom.: 2488

Bravo AF: 0.454

Asia WGS AF: 0.546 AC: 1898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.82

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: rs2301335; hg19: chr7-130132826;