rs28599926

Variant names:

• chr15-22225320-C-T
• rs28599926
• ENST00000408714.1:n.10G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000408714.1(MIR1268A):​n.10G>A 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 0.137 in 143,430 control chromosomes in the GnomAD database, including 247 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 0.14 (247 hom., cov: 40)
  • Exomes 𝑓: 0.034 (0 hom.)
• Consequence: MIR1268A ENST00000408714.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.742
• Publications: 15 publications found

Genes affected

MIR1268A (HGNC:35336): (microRNA 1268a) 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]

ENSG00000308335 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS2: High Homozygotes in GnomAd4 at 247 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR1268A	NR_031672.1	n.10G>A		non_coding_transcript_exon_variant	Exon 1 of 1
MIR1268A	unassigned_transcript_2657	n.6G>A		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR1268A	ENST00000408714.1	n.10G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000308335	ENST00000833384.1	n.274+14276G>A		intron_variant	Intron 2 of 2
ENSG00000308335	ENST00000833385.1	n.448+14276G>A		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.138 AC: 19582 AN: 142048 Hom.: 244 Cov.: 40

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0644

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0924

Gnomad MID AF: 0.0671

Gnomad NFE AF: 0.0589

Gnomad OTH AF: 0.123

GnomAD2 exomes AF: 0.0484 AC: 3 AN: 62 AF XY: 0.0909

Gnomad AFR exome AF: 0.250

Gnomad AMR exome AF: 0.00

Gnomad FIN exome AF: 0.100

Gnomad NFE exome AF: 0.0238

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0343 AC: 44 AN: 1282 Hom.: 0 Cov.: 0 AF XY: 0.0322 AC XY: 29 AN XY: 902

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

African (AFR) AF: 0.222 AC: 8 AN: 36

American (AMR) AF: 0.00 AC: 0 AN: 10

Ashkenazi Jewish (ASJ) AF: 0.0625 AC: 1 AN: 16

East Asian (EAS) AF: 0.0588 AC: 2 AN: 34

South Asian (SAS) AF: 0.0313 AC: 1 AN: 32

European-Finnish (FIN) AF: 0.0500 AC: 1 AN: 20

Middle Eastern (MID) AF: 0.00847 AC: 1 AN: 118

European-Non Finnish (NFE) AF: 0.0267 AC: 25 AN: 936

Other (OTH) AF: 0.0625 AC: 5 AN: 80

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.138 AC: 19627 AN: 142148 Hom.: 247 Cov.: 40 AF XY: 0.139 AC XY: 9638 AN XY: 69396

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

African (AFR) AF: 0.290 AC: 10847 AN: 37366

American (AMR) AF: 0.126 AC: 1845 AN: 14612

Ashkenazi Jewish (ASJ) AF: 0.0644 AC: 213 AN: 3306

East Asian (EAS) AF: 0.239 AC: 1140 AN: 4766

South Asian (SAS) AF: 0.112 AC: 495 AN: 4436

European-Finnish (FIN) AF: 0.0924 AC: 908 AN: 9826

Middle Eastern (MID) AF: 0.0761 AC: 21 AN: 276

European-Non Finnish (NFE) AF: 0.0589 AC: 3813 AN: 64706

Other (OTH) AF: 0.124 AC: 248 AN: 2004

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.118 Hom.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	10
DANN	Benign	0.57
PhyloP100		0.74
Mutation Taster		=96/4	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs28599926; hg19: chr15-22513271;