rs61992670

Variant names:

• chr14-101065396-C-T
• rs61992670
• ENST00000699461.1:n.496+3789C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000699461.1(MEG9):​n.496+3789C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 529,966 control chromosomes in the GnomAD database, including 456 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 0.031 (134 hom., cov: 32)
  • Exomes 𝑓: 0.035 (322 hom.)
• Consequence: MEG9 ENST00000699461.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.189
• Publications: 13 publications found

Genes affected

MEG9 (HGNC:43874): (maternally expressed 9)

MIR412 (HGNC:32064): (microRNA 412) 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 RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR369 (HGNC:31783): (microRNA 369) 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 RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR409 (HGNC:32055): (microRNA 409) 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 RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0519 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000699461.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR369	NR_029862.1		n.-202C>T		upstream_gene	N/A
	MIR412	NR_030155.1		n.-51C>T		upstream_gene	N/A
	MIR409	NR_029975.1		n.*18C>T		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEG9	ENST00000699461.1		n.496+3789C>T		intron	N/A
	MEG9	ENST00000699462.1		n.219+1029C>T		intron	N/A
	MEG9	ENST00000818609.1		n.258+1029C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0308 AC: 4683 AN: 152116 Hom.: 134 Cov.: 32

Gnomad AFR AF: 0.00845

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.0271

Gnomad ASJ AF: 0.0880

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0130

Gnomad FIN AF: 0.0231

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0463

Gnomad OTH AF: 0.0373

GnomAD2 exomes AF: 0.0329 AC: 8254 AN: 251060 AF XY: 0.0335

Gnomad AFR exome AF: 0.00938

Gnomad AMR exome AF: 0.0175

Gnomad ASJ exome AF: 0.0902

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0231

Gnomad NFE exome AF: 0.0475

Gnomad OTH exome AF: 0.0367

GnomAD4 exome AF: 0.0347 AC: 13100 AN: 377732 Hom.: 322 Cov.: 0 AF XY: 0.0336 AC XY: 7199 AN XY: 214222

African (AFR) AF: 0.0102 AC: 106 AN: 10432

American (AMR) AF: 0.0170 AC: 617 AN: 36250

Ashkenazi Jewish (ASJ) AF: 0.0895 AC: 1048 AN: 11706

East Asian (EAS) AF: 0.00 AC: 0 AN: 12994

South Asian (SAS) AF: 0.0158 AC: 1054 AN: 66692

European-Finnish (FIN) AF: 0.0250 AC: 808 AN: 32294

Middle Eastern (MID) AF: 0.0592 AC: 168 AN: 2836

European-Non Finnish (NFE) AF: 0.0458 AC: 8607 AN: 187988

Other (OTH) AF: 0.0418 AC: 692 AN: 16540

GnomAD4 genome AF: 0.0308 AC: 4685 AN: 152234 Hom.: 134 Cov.: 32 AF XY: 0.0292 AC XY: 2171 AN XY: 74434

African (AFR) AF: 0.00842 AC: 350 AN: 41550

American (AMR) AF: 0.0273 AC: 417 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0880 AC: 305 AN: 3464

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.0131 AC: 63 AN: 4824

European-Finnish (FIN) AF: 0.0231 AC: 245 AN: 10614

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0463 AC: 3151 AN: 68008

Other (OTH) AF: 0.0365 AC: 77 AN: 2112

Alfa AF: 0.0420 Hom.: 225

Bravo AF: 0.0305

Asia WGS AF: 0.00491 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.95
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs61992670; hg19: chr14-101531733;