rs3807348

Variant names:

• chr7-130496266-G-A
• rs3807348
• NM_002402.4:c.181+744G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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=-0.88).
• 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 rank	MANE	Protein	UniProt
MEST	NM_002402.4	c.181+744G>A		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.181+744G>A		intron_variant	Intron 2 of 11	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

African (AFR) AF: 0.254 AC: 1424 AN: 5608

American (AMR) AF: 0.543 AC: 7784 AN: 14332

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 5091 AN: 9744

East Asian (EAS) AF: 0.602 AC: 4668 AN: 7756

South Asian (SAS) AF: 0.484 AC: 25407 AN: 52504

European-Finnish (FIN) AF: 0.564 AC: 12164 AN: 21580

Middle Eastern (MID) AF: 0.386 AC: 408 AN: 1058

European-Non Finnish (NFE) AF: 0.554 AC: 82849 AN: 149614

Other (OTH) AF: 0.531 AC: 6687 AN: 12594

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

African (AFR) AF: 0.269 AC: 11140 AN: 41474

American (AMR) AF: 0.537 AC: 8203 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1869 AN: 3468

East Asian (EAS) AF: 0.597 AC: 3086 AN: 5170

South Asian (SAS) AF: 0.497 AC: 2394 AN: 4820

European-Finnish (FIN) AF: 0.564 AC: 5952 AN: 10548

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37523 AN: 67938

Other (OTH) AF: 0.481 AC: 1016 AN: 2112

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
PhyloP100		-0.012
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: rs3807348; hg19: chr7-130136107; COSMIC: COSV56230456; COSMIC: COSV56230456;