rs41272366

Variant names:

• chr7-130496224-T-A
• rs41272366
• NM_002402.4:c.181+702T>A

Your query was ambiguous. Multiple possible variants found:

• chr7-130496224-T-A
• chr7-130496224-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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:):

MIR335 (HGNC:31773): (microRNA 335) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The encoded miRNA is dysregulated in a variety of cancers, including breast, colorectal, and prostate cancer. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2017]

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2351 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002402.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEST	NM_002402.4	MANE Select	c.181+702T>A		intron	N/A	NP_002393.2
	MEST	NM_177524.2		c.154+702T>A		intron	N/A	NP_803490.1
	MEST	NM_177525.2		c.154+702T>A		intron	N/A	NP_803491.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEST	ENST00000223215.10	TSL:1 MANE Select	c.181+702T>A		intron	N/A	ENSP00000223215.4
	MEST	ENST00000341441.9	TSL:1	c.154+702T>A		intron	N/A	ENSP00000342749.4
	MEST	ENST00000416162.7	TSL:1	c.154+702T>A		intron	N/A	ENSP00000408933.2

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

GnomAD2 exomes AF: 0.0194 AC: 2629 AN: 135616 AF XY: 0.0215

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 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

African (AFR) AF: 0.00353 AC: 25 AN: 7082

American (AMR) AF: 0.00893 AC: 192 AN: 21492

Ashkenazi Jewish (ASJ) AF: 0.0301 AC: 322 AN: 10688

East Asian (EAS) AF: 0.000121 AC: 1 AN: 8232

South Asian (SAS) AF: 0.0430 AC: 2374 AN: 55204

European-Finnish (FIN) AF: 0.0110 AC: 287 AN: 26164

Middle Eastern (MID) AF: 0.0317 AC: 37 AN: 1168

European-Non Finnish (NFE) AF: 0.0203 AC: 3135 AN: 154532

Other (OTH) AF: 0.0194 AC: 261 AN: 13460

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

African (AFR) AF: 0.00404 AC: 168 AN: 41588

American (AMR) AF: 0.0114 AC: 174 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0280 AC: 97 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.0378 AC: 182 AN: 4816

European-Finnish (FIN) AF: 0.00923 AC: 98 AN: 10622

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0211 AC: 1434 AN: 68034

Other (OTH) AF: 0.0175 AC: 37 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.90
PhyloP100		2.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs41272366; hg19: chr7-130136065;