7-130497061-G-T

Variant names:

• chr7-130497061-G-T
• rs2072573
• NM_002402.4:c.182-95G>T

Variant summary

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

The NM_002402.4(MEST):​c.182-95G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 983,648 control chromosomes in the GnomAD database, including 140,216 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 (17947 hom., cov: 33)
  • Exomes 𝑓: 0.54 (122269 hom.)
• Consequence: MEST NM_002402.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.696

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEST	NM_002402.4	c.182-95G>T		intron_variant	Intron 2 of 11	ENST00000223215.10	NP_002393.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEST	ENST00000223215.10	c.182-95G>T		intron_variant	Intron 2 of 11	1	NM_002402.4	ENSP00000223215.4

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70514 AN: 151944 Hom.: 17939 Cov.: 33

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.476

GnomAD4 exome AF: 0.537 AC: 446954 AN: 831586 Hom.: 122269 Cov.: 11 AF XY: 0.535 AC XY: 228104 AN XY: 426692

Gnomad4 AFR exome AF: 0.231

Gnomad4 AMR exome AF: 0.525

Gnomad4 ASJ exome AF: 0.512

Gnomad4 EAS exome AF: 0.608

Gnomad4 SAS exome AF: 0.479

Gnomad4 FIN exome AF: 0.559

Gnomad4 NFE exome AF: 0.551

Gnomad4 OTH exome AF: 0.515

GnomAD4 genome AF: 0.464 AC: 70559 AN: 152062 Hom.: 17947 Cov.: 33 AF XY: 0.467 AC XY: 34697 AN XY: 74340

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.540

Gnomad4 EAS AF: 0.597

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.565

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.473

Alfa AF: 0.431 Hom.: 2466

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	-0.97
CADD	Benign	9.2
DANN	Benign	0.60

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: rs2072573; hg19: chr7-130136902;