20-26208276-A-C

Variant names:

• chr20-26208276-A-C
• rs7266947
• ENST00000427348.5:n.111+847T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000427348.5(MIR663AHG):​n.111+847T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0018 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MIR663AHG ENST00000427348.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 9 publications found

Genes affected

MIR663AHG (HGNC:27662): (MIR663A host gene)

MIR663A (HGNC:32919): (microRNA 663a) 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR663A	NR_030386.1	n.3T>G		non_coding_transcript_exon_variant	Exon 1 of 1
MIR663AHG	NR_040095.1	n.111+847T>G		intron_variant	Intron 1 of 4
MIR663A	unassigned_transcript_3435	n.-12T>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR663AHG	ENST00000427348.5	n.111+847T>G		intron_variant	Intron 1 of 4	1
MIR663A	ENST00000385250.1	n.3T>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
MIR663AHG	ENST00000432499.6	n.41+723T>G		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.00176 AC: 103 AN: 58460 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000511

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00143

Gnomad ASJ AF: 0.00515

Gnomad EAS AF: 0.00243

Gnomad SAS AF: 0.00254

Gnomad FIN AF: 0.00165

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00291

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 57094 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000138 AC: 19 AN: 138038 Hom.: 0 Cov.: 0 AF XY: 0.000122 AC XY: 10 AN XY: 82282

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000417 AC: 1 AN: 2396

American (AMR) AF: 0.000395 AC: 4 AN: 10138

Ashkenazi Jewish (ASJ) AF: 0.000175 AC: 1 AN: 5728

East Asian (EAS) AF: 0.00 AC: 0 AN: 1236

South Asian (SAS) AF: 0.0000966 AC: 3 AN: 31048

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6810

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 994

European-Non Finnish (NFE) AF: 0.000136 AC: 10 AN: 73468

Other (OTH) AF: 0.00 AC: 0 AN: 6220

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00176 AC: 103 AN: 58516 Hom.: 0 Cov.: 0 AF XY: 0.00178 AC XY: 51 AN XY: 28622

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000509 AC: 11 AN: 21602

American (AMR) AF: 0.00143 AC: 8 AN: 5582

Ashkenazi Jewish (ASJ) AF: 0.00515 AC: 7 AN: 1358

East Asian (EAS) AF: 0.00243 AC: 4 AN: 1646

South Asian (SAS) AF: 0.00254 AC: 4 AN: 1572

European-Finnish (FIN) AF: 0.00165 AC: 7 AN: 4232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 142

European-Non Finnish (NFE) AF: 0.00291 AC: 62 AN: 21270

Other (OTH) AF: 0.00 AC: 0 AN: 786

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.512 Hom.: 5508

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.7
DANN	Benign	0.54
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs7266947; hg19: chr20-26188912; COSMIC: COSV101155723;