rs12338528

Variant names:

• chr9-94175707-G-A
• rs12338528
• ENST00000602703.1:n.93+9326G>A

Variant summary

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

The ENST00000602703.1(MIRLET7A1HG):​n.93+9326G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0323 in 152,064 control chromosomes in the GnomAD database, including 265 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 0.032 (265 hom., cov: 33)
• Consequence: MIRLET7A1HG ENST00000602703.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374

Genes affected

MIRLET7A1HG (HGNC:53970): (miRlet-7a-1/let-7f-1/let-7d cluster host gene)

MIRLET7A1 (HGNC:31476): (microRNA let-7a-1) 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIRLET7A1HG	NR_170274.1	n.125-158G>A		intron_variant	Intron 1 of 1
MIRLET7A1HG	NR_170275.1	n.124+9326G>A		intron_variant	Intron 1 of 1
MIRLET7A1HG	NR_170276.1	n.125-158G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIRLET7A1HG	ENST00000602703.1	n.93+9326G>A		intron_variant	Intron 1 of 1	3
MIRLET7A1HG	ENST00000652620.1	n.117-158G>A		intron_variant	Intron 1 of 4
MIRLET7A1HG	ENST00000652769.2	n.125-158G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0322 AC: 4900 AN: 151946 Hom.: 264 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00970

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.0216

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0323 AC: 4912 AN: 152064 Hom.: 265 Cov.: 33 AF XY: 0.0319 AC XY: 2372 AN XY: 74338

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.00969

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000750

Gnomad4 OTH AF: 0.0214

Alfa AF: 0.0255 Hom.: 24

Bravo AF: 0.0373

Asia WGS AF: 0.00779 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.5
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12338528; hg19: chr9-96937989;