rs6997249

Positions:

• chr8-129484119-G-A

Variant summary

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

The NR_037457.1(MIR3686):​n.24C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 154,620 control chromosomes in the GnomAD database, including 6,402 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 0.28 (6295 hom., cov: 32)
  • Exomes 𝑓: 0.28 (107 hom.)
• Consequence: MIR3686 NR_037457.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

Genes affected

MIR3686 (HGNC:38887): (microRNA 3686) 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]

CCDC26 (HGNC:28416): (CCDC26 long non-coding RNA)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIR3686	NR_037457.1	n.24C>T		non_coding_transcript_exon_variant	1/1
CCDC26	NR_130917.1	n.313-3429C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIR3686	ENST00000577904.1	n.24C>T		non_coding_transcript_exon_variant	1/1
CCDC26	ENST00000675388.1	n.135-3429C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42090 AN: 151980 Hom.: 6293 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.269

GnomAD3 exomes AF: 0.298 AC: 1583 AN: 5318 Hom.: 228 AF XY: 0.315 AC XY: 791 AN XY: 2508

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.264

Gnomad ASJ exome AF: 0.327

Gnomad EAS exome AF: 0.0469

Gnomad SAS exome AF: 0.173

Gnomad NFE exome AF: 0.312

Gnomad OTH exome AF: 0.218

GnomAD4 exome AF: 0.280 AC: 707 AN: 2522 Hom.: 107 Cov.: 0 AF XY: 0.298 AC XY: 391 AN XY: 1310

Gnomad4 AFR exome AF: 0.237

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.500

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.400

Gnomad4 NFE exome AF: 0.287

Gnomad4 OTH exome AF: 0.253

GnomAD4 genome AF: 0.277 AC: 42103 AN: 152098 Hom.: 6295 Cov.: 32 AF XY: 0.279 AC XY: 20775 AN XY: 74354

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.268

Alfa AF: 0.317 Hom.: 988

Bravo AF: 0.266

Asia WGS AF: 0.149 AC: 518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.8
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6997249; hg19: chr8-130496365;