8-142176399-G-C

Position:

• chr8-142176399-G-C

Variant summary

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

The NR_039682.1(MIR4472-1):​n.61G>C 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 0.217 in 154,140 control chromosomes in the GnomAD database, including 5,534 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 0.22 (5515 hom., cov: 32)
  • Exomes 𝑓: 0.094 (19 hom.)
• Consequence: MIR4472-1 NR_039682.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.984

Genes affected

MIR4472-1 (HGNC:41644): (microRNA 4472-1) 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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR4472-1	NR_039682.1	n.61G>C		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR4472-1	ENST00000584349.1	n.61G>C		mature_miRNA_variant	1/1
	ENST00000662748.1	n.366+8763C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33211 AN: 151838 Hom.: 5502 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.171

GnomAD3 exomes AF: 0.0939 AC: 34 AN: 362 Hom.: 1 AF XY: 0.0941 AC XY: 19 AN XY: 202

Gnomad AFR exome AF: 0.500

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0954

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0939 AC: 205 AN: 2184 Hom.: 19 Cov.: 0 AF XY: 0.106 AC XY: 116 AN XY: 1092

Gnomad4 AFR exome AF: 0.419

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.0909

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.193

GnomAD4 genome AF: 0.219 AC: 33271 AN: 151956 Hom.: 5515 Cov.: 32 AF XY: 0.219 AC XY: 16248 AN XY: 74318

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.170

Alfa AF: 0.0849 Hom.: 150

Bravo AF: 0.236

Asia WGS AF: 0.177 AC: 614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28655823; hg19: chr8-143257760;