chr7-130504561-C-G

Variant names:

• chr7-130504561-C-G
• rs1005171
• NM_002402.4:c.891-378C>G

Variant summary

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

The NM_002402.4(MEST):​c.891-378C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 152,048 control chromosomes in the GnomAD database, including 17,521 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 0.45 (17521 hom., cov: 32)
• Consequence: MEST NM_002402.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEST	NM_002402.4	c.891-378C>G		intron_variant	Intron 11 of 11	ENST00000223215.10	NP_002393.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEST	ENST00000223215.10	c.891-378C>G		intron_variant	Intron 11 of 11	1	NM_002402.4	ENSP00000223215.4

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69139 AN: 151930 Hom.: 17514 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.455 AC: 69181 AN: 152048 Hom.: 17521 Cov.: 32 AF XY: 0.458 AC XY: 34046 AN XY: 74286

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.464

Alfa AF: 0.489 Hom.: 2447

Bravo AF: 0.443

Asia WGS AF: 0.543 AC: 1887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.3
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: rs1005171; hg19: chr7-130144402;